Skip to main content
SpringerLink
Log in

Knockout Mouse Models Provide Insight into the Biological Functions of CRL1 Components

  • Chapter
  • First Online:
Cullin-RING Ligases and Protein Neddylation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1217))

Abstract

The CRL1 complex, also known as the SCF complex, is a ubiquitin ligase that in mammals consists of an adaptor protein (SKP1), a scaffold protein (CUL1), a RING finger protein (RBX1, also known as ROC1), and one of about 70 F-box proteins. Given that the F-box proteins determine the substrate specificity of the CRL1 complex, the variety of these proteins allows the generation of a large number of ubiquitin ligases that promote the degradation or regulate the function of many substrate proteins and thereby control numerous key cellular processes. The physiological and pathological functions of these many CRL1 ubiquitin ligases have been studied by the generation and characterization of knockout mouse models that lack specific CRL1 components. In this chapter, we provide a comprehensive overview of these mouse models and discuss the role of each CRL1 component in mouse physiology and pathology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

APC/C:

Anaphase-promoting complex/cyclosome

ASK1:

Apoptotic signal-regulating kinase 1

BACE1:

β-site amyloid precursor protein-cleaving enzyme 1

BMP:

Bone morphogenetic protein

CDK1:

Cyclin-dependent kinase 1

CML:

Chronic myeloid leukemia

CP110:

Centrosomal protein 110

CRL:

Cullin-RING ubiquitin ligase

CRY:

Cryptochrome

CUL1:

Cullin-1

DiPIUS:

Differential proteomics-based identification of ubiquitylation substrates

DKO:

Double knockout

DP:

Double positive

EMI1:

Early mitotic inhibitor 1

EMI2:

Early mitotic inhibitor 2

F-box:

Cyclin F-box

FBXL:

LRR-containing F-box proteins

FBXO:

Other domain-containing F-box proteins

FBXW:

WD40 domain-containing F-box proteins

GC:

Germinal center

GSTP1:

Glutathione S-transferase π1

HECT:

Homologous to E6-associated protein C-terminus

HSC:

Hematopoietic stem cell

IRE:

Iron-responsive element

IRP:

Iron-regulatory protein

JNK:

c-Jun NH2-terminal kinase

KO:

Knockout

LAP:

Leukemia-associated protein

LIC:

Leukemia-initiating cell

LRR:

Leucine-rich repeat

MAFbx:

Muscle atrophy F-box protein

MAPK:

Mitogen-activated protein kinase

mTOR:

Mammalian target of rapamycin

NASH:

Nonalcoholic steatohepatitis

NSPC:

Neural stem/progenitor cell

PD-1:

Programmed cell death-1

PD-L1:

Programmed cell death-ligand 1

PER:

Period

PHD:

Plant homeodomain

PI3K:

Phosphoinositide 3-kinase

PRC:

Polycomb repressive complex

PTEN:

Phosphatase and tensin homolog

RBR:

RING between RING

RBX1:

RING box 1, also known as regulator of Cullins 1 or ROC1

RIM1:

Rab3-interacting molecule 1

RING:

Really interesting new gene

ROS:

Reactive oxygen species

RRM2:

Ribonucleotide reductase 2

SASP:

Senescence-associated secretory phenotype

SCF:

SKP1–CUL1–F-box protein

Scg2:

Secretogranin 2

SKP1:

S-phase kinase-associated protein 1

SKP2:

S-phase kinase-associated protein 2

SREBP:

Sterol regulatory element-binding protein

SSC:

Spermatogonial stem cell

T-ALL:

T-cell acute lymphoblastic leukemia

U-box:

UFD2-box

β-TrCP:

β-transducin repeat-containing protein

References

  • Adams D, Baldock R, Bhattacharya S, Copp AJ, Dickinson M, Greene ND, Henkelman M, Justice M, Mohun T, Murray SA et al (2013) Bloomsbury report on mouse embryo phenotyping: recommendations from the IMPC workshop on embryonic lethal screening. Dis Model Mech 6:571–579

    Article  PubMed  PubMed Central  Google Scholar 

  • Akhoondi S, Sun D, von der Lehr N, Apostolidou S, Klotz K, Maljukova A, Cepeda D, Fiegl H, Dafou D, Marth C et al (2007) FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res 67:9006–9012

    CAS  PubMed  Google Scholar 

  • Andricovich J, Kai Y, Peng W, Foudi A, Tzatsos A (2016) Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis. J Clin Invest 126:905–920

    Article  PubMed  PubMed Central  Google Scholar 

  • Arabi A, Ullah K, Branca RM, Johansson J, Bandarra D, Haneklaus M, Fu J, Aries I, Nilsson P, Den Boer ML et al (2012) Proteomic screen reveals Fbw7 as a modulator of the NF-kappaB pathway. Nat Commun 3:976

    Article  PubMed  CAS  Google Scholar 

  • Arai T, Kasper JS, Skaar JR, Ali SH, Takahashi C, DeCaprio JA (2003) Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis. Proc Natl Acad Sci U S A 100:9855–9860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Babaei-Jadidi R, Li N, Saadeddin A, Spencer-Dene B, Jandke A, Muhammad B, Ibrahim EE, Muraleedharan R, Abuzinadah M, Davis H et al (2011) FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. J Exp Med 208:295–312

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baguma-Nibasheka M, Kablar B (2009) Abnormal retinal development in the Btrc null mouse. Dev Dyn 238:2680–2687

    Article  PubMed  PubMed Central  Google Scholar 

  • Bai C, Richman R, Elledge SJ (1994) Human cyclin F. EMBO J 13:6087–6098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bai L, Chen MM, Chen ZD, Zhang P, Tian S, Zhang Y, Zhu XY, Liu Y, She ZG, Ji YX et al (2019) F-box/WD repeat-containing protein 5 mediates the ubiquitination of apoptosis signal-regulating kinase 1 and exacerbates nonalcoholic steatohepatitis in mice. Hepatology

    Google Scholar 

  • Barbash O, Zamfirova P, Lin DI, Chen X, Yang K, Nakagawa H, Lu F, Rustgi AK, Diehl JA (2008) Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer. Cancer Cell 14:68–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bodine SC, Baehr LM (2014) Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab 307:E469–E484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K et al (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:1704–1708

    Article  CAS  PubMed  Google Scholar 

  • Boulard M, Edwards JR, Bestor TH (2016) Abnormal X chromosome inactivation and sex-specific gene dysregulation after ablation of FBXL10. Epigenetics Chromatin 9:22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Busino L, Bassermann F, Maiolica A, Lee C, Nolan PM, Godinho SI, Draetta GF, Pagano M (2007) SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science 316:900–904

    Article  CAS  PubMed  Google Scholar 

  • Busino L, Millman SE, Scotto L, Kyratsous CA, Basrur V, O’Connor O, Hoffmann A, Elenitoba-Johnson KS, Pagano M (2012) Fbxw7alpha- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nat Cell Biol 14:375–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camaschella C (2015) Iron-deficiency anemia. N Engl J Med 372:1832–1843

    Article  PubMed  Google Scholar 

  • Cattoretti G, Pasqualucci L, Ballon G, Tam W, Nandula SV, Shen Q, Mo T, Murty VV, Dalla-Favera R (2005) Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice. Cancer Cell 7:445–455

    Article  CAS  PubMed  Google Scholar 

  • D’Alessandro M, Beesley S, Kim JK, Jones Z, Chen R, Wi J, Kyle K, Vera D, Pagano M, Nowakowski R et al (2017) Stability of wake-sleep cycles requires robust degradation of the PERIOD protein. Curr Biol 27:3454–3467 e3458

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • D’Angiolella V, Esencay M, Pagano M (2013) A cyclin without cyclin-dependent kinases: cyclin F controls genome stability through ubiquitin-mediated proteolysis. Trends Cell Biol 23:135–140

    Article  PubMed  CAS  Google Scholar 

  • Davis RJ, Welcker M, Clurman BE (2014) Tumor suppression by the Fbw7 ubiquitin ligase: mechanisms and opportunities. Cancer Cell 26:455–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dealy MJ, Nguyen KV, Lo J, Gstaiger M, Krek W, Elson D, Arbeit J, Kipreos ET, Johnson RS (1999) Loss of Cul1 results in early embryonic lethality and dysregulation of cyclin E. Nat Genet 23:245–248

    Article  CAS  PubMed  Google Scholar 

  • Deshaies RJ, Joazeiro CA (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78:399–434

    Article  CAS  PubMed  Google Scholar 

  • Duan S, Cermak L, Pagan JK, Rossi M, Martinengo C, di Celle PF, Chapuy B, Shipp M, Chiarle R, Pagano M (2012) FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature 481:90–93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erhardt JA, Hynicka W, DiBenedetto A, Shen N, Stone N, Paulson H, Pittman RN (1998) A novel F box protein, NFB42, is highly enriched in neurons and induces growth arrest. J Biol Chem 273:35222–35227

    Article  CAS  PubMed  Google Scholar 

  • FeiFei W, HongHai X, YongRong Y, PingXiang W, JianHua W, XiaoHui Z, JiaoYing L, JingBo S, Kun Z, XiaoLi R et al (2019) FBX8 degrades GSTP1 through ubiquitination to suppress colorectal cancer progression. Cell Death Dis 10:351

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fleming RE, Ponka P (2012) Iron overload in human disease. N Engl J Med 366:348–359

    Article  CAS  PubMed  Google Scholar 

  • Fodde R (2002) The APC gene in colorectal cancer. Eur J Cancer 38:867–871

    Article  CAS  PubMed  Google Scholar 

  • Frescas D, Pagano M (2008) Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nat Rev Cancer 8:438–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fritzen D, Kuechler A, Grimmel M, Becker J, Peters S, Sturm M, Hundertmark H, Schmidt A, Kreiss M, Strom TM et al (2018) De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies. Hum Genet 137:401–411

    Article  CAS  PubMed  Google Scholar 

  • Fukuda T, Tokunaga A, Sakamoto R, Yoshida N (2011) Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly. Mol Cell Neurosci 46:614–624

    Article  CAS  PubMed  Google Scholar 

  • Fukushima H, Matsumoto A, Inuzuka H, Zhai B, Lau AW, Wan L, Gao D, Shaik S, Yuan M, Gygi SP et al (2012) SCF(Fbw7) modulates the NFkB signaling pathway by targeting NFkB2 for ubiquitination and destruction. Cell Rep 1:434–443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Godinho SI, Maywood ES, Shaw L, Tucci V, Barnard AR, Busino L, Pagano M, Kendall R, Quwailid MM, Romero MR et al (2007) The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science 316:897–900

    Article  CAS  PubMed  Google Scholar 

  • Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A 98:14440–14445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gong B, Chen F, Pan Y, Arrieta-Cruz I, Yoshida Y, Haroutunian V, Pasinetti GM (2010) SCFFbx2-E3-ligase-mediated degradation of BACE1 attenuates Alzheimer’s disease amyloidosis and improves synaptic function. Aging Cell 9:1018–1031

    Article  CAS  PubMed  Google Scholar 

  • Gopinathan L, Szmyd R, Low D, Diril MK, Chang HY, Coppola V, Liu K, Tessarollo L, Guccione E, van Pelt AMM et al (2017) Emi2 is essential for mouse spermatogenesis. Cell Rep 20:697–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gregor A, Sadleir LG, Asadollahi R, Azzarello-Burri S, Battaglia A, Ousager LB, Boonsawat P, Bruel AL, Buchert R, Calpena E et al (2018) De Novo variants in the F-box protein FBXO11 in 20 individuals with a variable neurodevelopmental disorder. Am J Hum Genet 103:305–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grim JE, Knoblaugh SE, Guthrie KA, Hagar A, Swanger J, Hespelt J, Delrow JJ, Small T, Grady WM, Nakayama KI et al (2012) Fbw7 and p53 cooperatively suppress advanced and chromosomally unstable intestinal cancer. Mol Cell Biol 32:2160–2167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L, Donzelli M, Margottin-Goguet F, Jackson PK, Yamasaki L, Pagano M (2003) Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Dev Cell 4:799–812

    Article  CAS  PubMed  Google Scholar 

  • Hardisty RE, Erven A, Logan K, Morse S, Guionaud S, Sancho-Oliver S, Hunter AJ, Brown SD, Steel KP (2003) The deaf mouse mutant Jeff (Jf) is a single gene model of otitis media. J Assoc Res Otolaryngol 4:130–138

    Article  PubMed  Google Scholar 

  • Hardisty-Hughes RE, Tateossian H, Morse SA, Romero MR, Middleton A, Tymowska-Lalanne Z, Hunter AJ, Cheeseman M, Brown SD (2006) A mutation in the F-box gene, Fbxo11, causes otitis media in the Jeff mouse. Hum Mol Genet 15:3273–3279

    Article  CAS  PubMed  Google Scholar 

  • Hentze MW, Muckenthaler MU, Galy B, Camaschella C (2010) Two to tango: regulation of Mammalian iron metabolism. Cell 142:24–38

    Article  CAS  PubMed  Google Scholar 

  • Hinds P, Pietruska J (2017) Senescence and tumor suppression. F1000Res 6:2121

    Article  PubMed  PubMed Central  Google Scholar 

  • Hirano A, Yumimoto K, Tsunematsu R, Matsumoto M, Oyama M, Kozuka-Hata H, Nakagawa T, Lanjakornsiripan D, Nakayama KI, Fukada Y (2013) FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes. Cell 152:1106–1118

    Article  CAS  PubMed  Google Scholar 

  • Hoeck JD, Jandke A, Blake SM, Nye E, Spencer-Dene B, Brandner S, Behrens A (2010) Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun. Nat Neurosci 13:1365–1372

    Article  CAS  PubMed  Google Scholar 

  • Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser RS, Zhai B, Wan L, Gutierrez A, Lau AW et al (2011) SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature 471:104–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jansen S, van der Werf IM, Innes AM, Afenjar A, Agrawal PB, Anderson IJ, Atwal PS, van Binsbergen E, van den Boogaard MJ, Castiglia L et al (2019) De novo variants in FBXO11 cause a syndromic form of intellectual disability with behavioral problems and dysmorphisms. Eur J Hum Genet

    Google Scholar 

  • Jin J, Cardozo T, Lovering RC, Elledge SJ, Pagano M, Harper JW (2004) Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev 18:2573–2580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johmura Y, Sun J, Kitagawa K, Nakanishi K, Kuno T, Naiki-Ito A, Sawada Y, Miyamoto T, Okabe A, Aburatani H et al (2016) SCF(Fbxo22)-KDM4A targets methylated p53 for degradation and regulates senescence. Nat Commun 7:10574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386:896–912

    Article  CAS  PubMed  Google Scholar 

  • Kanarek N, Horwitz E, Mayan I, Leshets M, Cojocaru G, Davis M, Tsuberi BZ, Pikarsky E, Pagano M, Ben-Neriah Y (2010) Spermatogenesis rescue in a mouse deficient for the ubiquitin ligase SCF{beta}-TrCP by single substrate depletion. Genes Dev 24:470–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanarek N, Grivennikov SI, Leshets M, Lasry A, Alkalay I, Horwitz E, Shaul YD, Stachler M, Voronov E, Apte RN et al (2014) Critical role for IL-1beta in DNA damage-induced mucositis. Proc Natl Acad Sci U S A 111:E702–E711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanatsu-Shinohara M, Onoyama I, Nakayama KI, Shinohara T (2014) Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates spermatogonial stem cell self-renewal. Proc Natl Acad Sci U S A 111:8826–8831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanie T, Onoyama I, Matsumoto A, Yamada M, Nakatsumi H, Tateishi Y, Yamamura S, Tsunematsu R, Matsumoto M, Nakayama KI (2012) Genetic reevaluation of the role of F-box proteins in cyclin D1 degradation. Mol Cell Biol 32:590–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato A, Rouach N, Nicoll RA, Bredt DS (2005) Activity-dependent NMDA receptor degradation mediated by retrotranslocation and ubiquitination. Proc Natl Acad Sci U S A 102:5600–5605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawakami E, Tokunaga A, Ozawa M, Sakamoto R, Yoshida N (2015) The histone demethylase Fbxl11/Kdm2a plays an essential role in embryonic development by repressing cell-cycle regulators. Mech Dev 135:31–42

    Article  CAS  PubMed  Google Scholar 

  • Kleiger G, Mayor T (2014) Perilous journey: a tour of the ubiquitin-proteasome system. Trends Cell Biol 24:352–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kossatz U, Dietrich N, Zender L, Buer J, Manns MP, Malek NP (2004) Skp2-dependent degradation of p27kip1 is essential for cell cycle progression. Genes Dev 18:2602–2607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koyama-Nasu R, David G, Tanese N (2007) The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun. Nat Cell Biol 9:1074–1080

    Article  CAS  PubMed  Google Scholar 

  • Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJ, Watanabe T (2015) Colorectal cancer. Nat Rev Dis Primers 1:15065

    Article  PubMed  PubMed Central  Google Scholar 

  • Kwon YW, Kim IJ, Wu D, Lu J, Stock WA Jr, Liu Y, Huang Y, Kang HC, DelRosario R, Jen KY et al (2012) Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development. Mol Cancer Res 10:834–844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lagirand-Cantaloube J, Offner N, Csibi A, Leibovitch MP, Batonnet-Pichon S, Tintignac LA, Segura CT, Leibovitch SA (2008) The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. EMBO J 27:1266–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lara-Gonzalez P, Kim T, Desai A (2017) Taming the beast: control of APC/C(Cdc20)-dependent destruction. Cold Spring Harb Symp Quant Biol 82:111–121

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee H, Lee DJ, Oh SP, Park HD, Nam HH, Kim JM, Lim DS (2006) Mouse emi1 has an essential function in mitotic progression during early embryogenesis. Mol Cell Biol 26:5373–5381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Pei XH, Yan J, Yan F, Cappell KM, Whitehurst AW, Xiong Y (2014) CUL9 mediates the functions of the 3M complex and ubiquitylates survivin to maintain genome integrity. Mol Cell 54:805–819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin DI, Barbash O, Kumar KG, Weber JD, Harper JW, Klein-Szanto AJ, Rustgi A, Fuchs SY, Diehl JA (2006) Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell 24:355–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin HK, Chen Z, Wang G, Nardella C, Lee SW, Chan CH, Yang WL, Wang J, Egia A, Nakayama KI et al (2010) Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature 464:374–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Wang Y, Du Z, Yan X, Zheng P, Liu Y (2016) Fbxo30 regulates mammopoiesis by targeting the bipolar mitotic kinesin Eg5. Cell Rep 15:1111–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madgwick S, Jones KT (2007) How eggs arrest at metaphase II: MPF stabilisation plus APC/C inhibition equals cytostatic factor. Cell Div 2:4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Malyukova A, Dohda T, von der Lehr N, Akhoondi S, Corcoran M, Heyman M, Spruck C, Grander D, Lendahl U, Sangfelt O (2007) The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling. Cancer Res 67:5611–5616

    Article  CAS  PubMed  Google Scholar 

  • Mao JH, Perez-Losada J, Wu D, Delrosario R, Tsunematsu R, Nakayama KI, Brown K, Bryson S, Balmain A (2004) Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature 432:775–779

    Article  CAS  PubMed  Google Scholar 

  • Marzio A, Puccini J, Kwon Y, Maverakis NK, Arbini A, Sung P, Bar-Sagi D, Pagano M (2019) The F-box domain-dependent activity of EMI1 regulates PARPi sensitivity in triple-negative breast cancers. Mol Cell 73:224–237 e226

    Article  CAS  PubMed  Google Scholar 

  • Maser RS, Choudhury B, Campbell PJ, Feng B, Wong KK, Protopopov A, O’Neil J, Gutierrez A, Ivanova E, Perna I et al (2007) Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 447:966–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumoto A, Onoyama I, Sunabori T, Kageyama R, Okano H, Nakayama KI (2011) Fbxw7-dependent degradation of Notch is required for control of “stemness” and neuronal-glial differentiation in neural stem cells. J Biol Chem 286:13754–13764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F, Takubo K, Mashimo Y, Oguro H, Nitta E, Ito K et al (2008) Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Genes Dev 22:986–991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng X, Liu X, Guo X, Jiang S, Chen T, Hu Z, Liu H, Bai Y, Xue M, Hu R et al (2018) FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells. Nature 564:130–135

    Article  CAS  PubMed  Google Scholar 

  • Metzger MB, Hristova VA, Weissman AM (2012) HECT and RING finger families of E3 ubiquitin ligases at a glance. J Cell Sci 125:531–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morohoshi A, Nakagawa T, Nakano S, Nagasawa Y, Nakayama K (2019) The ubiquitin ligase subunit beta-TrCP in Sertoli cells is essential for spermatogenesis in mice. Dev Biol 445:178–188

    Article  CAS  PubMed  Google Scholar 

  • Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama KI (2011) The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. Cell Metab 14:339–351

    Article  CAS  PubMed  Google Scholar 

  • Muckenthaler MU, Rivella S, Hentze MW, Galy B (2017) A red carpet for iron metabolism. Cell 168:344–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muto Y, Nishiyama M, Nita A, Moroishi T, Nakayama KI (2017) Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells. Nat Commun 8:16114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa T, Nakayama K (2015) Protein monoubiquitylation: targets and diverse functions. Genes Cells 20:543–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa T, Araki T, Nakagawa M, Hirao A, Unno M, Nakayama K (2015) S6 kinase- and beta-TrCP2-dependent degradation of p19Arf is required for cell proliferation. Mol Cell Biol 35:3517–3527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa T, Zhang T, Kushi R, Nakano S, Endo T, Nakagawa M, Yanagihara N, Zarkower D, Nakayama K (2017) Regulation of mitosis-meiosis transition by the ubiquitin ligase beta-TrCP in male germ cells. Development 144:4137–4147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6:369–381

    Article  CAS  PubMed  Google Scholar 

  • Nakayama K, Nagahama H, Minamishima YA, Matsumoto M, Nakamichi I, Kitagawa K, Shirane M, Tsunematsu R, Tsukiyama T, Ishida N et al (2000) Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J 19:2069–2081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakayama K, Hatakeyama S, Maruyama S, Kikuchi A, Onoe K, Good RA, Nakayama KI (2003) Impaired degradation of inhibitory subunit of NF-kappa B (I kappa B) and beta-catenin as a result of targeted disruption of the beta-TrCP1 gene. Proc Natl Acad Sci U S A 100:8752–8757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakayama K, Nagahama H, Minamishima YA, Miyake S, Ishida N, Hatakeyama S, Kitagawa M, Iemura S, Natsume T, Nakayama KI (2004) Skp2-mediated degradation of p27 regulates progression into mitosis. Dev Cell 6:661–672

    Article  CAS  PubMed  Google Scholar 

  • Nelson RF, Glenn KA, Zhang Y, Wen H, Knutson T, Gouvion CM, Robinson BK, Zhou Z, Yang B, Smith RJ et al (2007) Selective cochlear degeneration in mice lacking the F-box protein, Fbx2, a glycoprotein-specific ubiquitin ligase subunit. J Neurosci 27:5163–5171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishiyama M, Nita A, Yumimoto K, Nakayama KI (2015) FBXL12-mediated degradation of ALDH3 is essential for trophoblast differentiation during placental development. Stem Cells 33:3327–3340

    Article  CAS  PubMed  Google Scholar 

  • Nita A, Nishiyama M, Muto Y, Nakayama KI (2016) FBXL12 regulates T-cell differentiation in a cell-autonomous manner. Genes Cells 21:517–524

    Article  CAS  PubMed  Google Scholar 

  • Nolan PM, Peters J, Strivens M, Rogers D, Hagan J, Spurr N, Gray IC, Vizor L, Brooker D, Whitehill E et al (2000) A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nat Genet 25:440–443

    Article  CAS  PubMed  Google Scholar 

  • O’Neil J, Grim J, Strack P, Rao S, Tibbitts D, Winter C, Hardwick J, Welcker M, Meijerink JP, Pieters R et al (2007) FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med 204:1813–1824

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Okabe H, Lee SH, Phuchareon J, Albertson DG, McCormick F, Tetsu O (2006) A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation. PLoS One 1:e128

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Onoyama I, Tsunematsu R, Matsumoto A, Kimura T, de Alboran IM, Nakayama K, Nakayama KI (2007) Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis. J Exp Med 204:2875–2888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Onoyama I, Suzuki A, Matsumoto A, Tomita K, Katagiri H, Oike Y, Nakayama K, Nakayama KI (2011) Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. J Clin Invest 121:342–354

    Article  CAS  PubMed  Google Scholar 

  • Pear WS, Miller JP, Xu L, Pui JC, Soffer B, Quackenbush RC, Pendergast AM, Bronson R, Aster JC, Scott ML et al (1998) Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood 92:3780–3792

    Article  CAS  PubMed  Google Scholar 

  • Petroski MD, Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 6:9–20

    Article  CAS  PubMed  Google Scholar 

  • Piva R, Liu J, Chiarle R, Podda A, Pagano M, Inghirami G (2002) In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation. Mol Cell Biol 22:8375–8387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE (2017) Parkinson disease. Nat Rev Dis Primers 3:17013

    Article  PubMed  Google Scholar 

  • Rajagopalan H, Jallepalli PV, Rago C, Velculescu VE, Kinzler KW, Vogelstein B, Lengauer C (2004) Inactivation of hCDC4 can cause chromosomal instability. Nature 428:77–81

    Article  CAS  PubMed  Google Scholar 

  • Reavie L, Buckley SM, Loizou E, Takeishi S, Aranda-Orgilles B, Ndiaye-Lobry D, Abdel-Wahab O, Ibrahim S, Nakayama KI, Aifantis I (2013) Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression. Cancer Cell 23:362–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reitsma JM, Liu X, Reichermeier KM, Moradian A, Sweredoski MJ, Hess S, Deshaies RJ (2017) Composition and regulation of the cellular repertoire of SCF ubiquitin ligases. Cell 171:1326–1339 e1314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rotin D, Kumar S (2009) Physiological functions of the HECT family of ubiquitin ligases. Nat Rev Mol Cell Biol 10:398–409

    Article  CAS  PubMed  Google Scholar 

  • Rouault TA (2013) Iron metabolism in the CNS: implications for neurodegenerative diseases. Nat Rev Neurosci 14:551–564

    Article  CAS  PubMed  Google Scholar 

  • Saiga T, Fukuda T, Matsumoto M, Tada H, Okano HJ, Okano H, Nakayama KI (2009) Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal development. Mol Cell Biol 29:3529–3543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sancho R, Jandke A, Davis H, Diefenbacher ME, Tomlinson I, Behrens A (2010) F-box and WD repeat domain-containing 7 regulates intestinal cell lineage commitment and is a haploinsufficient tumor suppressor. Gastroenterology 139:929–941

    Article  CAS  PubMed  Google Scholar 

  • Santra MK, Wajapeyee N, Green MR (2009) F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature 459:722–725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schneider C, Kon N, Amadori L, Shen Q, Schwartz FH, Tischler B, Bossennec M, Dominguez-Sola D, Bhagat G, Gu W et al (2016) FBXO11 inactivation leads to abnormal germinal-center formation and lymphoproliferative disease. Blood 128:660–666

    Article  CAS  PubMed  Google Scholar 

  • Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348:56–61

    Article  CAS  PubMed  Google Scholar 

  • Shimizu K, Nihira NT, Inuzuka H, Wei W (2018) Physiological functions of FBW7 in cancer and metabolism. Cell Signal 46:15–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shojaee S, Sina F, Banihosseini SS, Kazemi MH, Kalhor R, Shahidi GA, Fakhrai-Rad H, Ronaghi M, Elahi E (2008) Genome-wide linkage analysis of a Parkinsonian-pyramidal syndrome pedigree by 500 K SNP arrays. Am J Hum Genet 82:1375–1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shoji S, Yoshida N, Amanai M, Ohgishi M, Fukui T, Fujimoto S, Nakano Y, Kajikawa E, Perry AC (2006) Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20. EMBO J 25:834–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siepka SM, Yoo SH, Park J, Song W, Kumar V, Hu Y, Lee C, Takahashi JS (2007) Circadian mutant overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression. Cell 129:1011–1023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smit JJ, Sixma TK (2014) RBR E3-ligases at work. EMBO Rep 15:142–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song JH, Schnittke N, Zaat A, Walsh CS, Miller CW (2008) FBXW7 mutation in adult T-cell and B-cell acute lymphocytic leukemias. Leuk Res 32:1751–1755

    Article  CAS  PubMed  Google Scholar 

  • Sparks AB, Morin PJ, Vogelstein B, Kinzler KW (1998) Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res 58:1130–1134

    CAS  PubMed  Google Scholar 

  • Sumida Y, Yoneda M (2018) Current and future pharmacological therapies for NAFLD/NASH. J Gastroenterol 53:362–376

    Article  CAS  PubMed  Google Scholar 

  • Swatek KN, Komander D (2016) Ubiquitin modifications. Cell Res 26:399–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tada H, Okano HJ, Takagi H, Shibata S, Yao I, Matsumoto M, Saiga T, Nakayama KI, Kashima H, Takahashi T et al (2010) Fbxo45, a novel ubiquitin ligase, regulates synaptic activity. J Biol Chem 285:3840–3849

    Article  CAS  PubMed  Google Scholar 

  • Takahashi JS (2017) Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 18:164–179

    Article  CAS  PubMed  Google Scholar 

  • Takeishi S, Nakayama KI (2016) To wake up cancer stem cells, or to let them sleep, that is the question. Cancer Sci 107:875–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeishi S, Matsumoto A, Onoyama I, Naka K, Hirao A, Nakayama KI (2013) Ablation of Fbxw7 eliminates leukemia-initiating cells by preventing quiescence. Cancer Cell 23:347–361

    Article  CAS  PubMed  Google Scholar 

  • Tan M, Davis SW, Saunders TL, Zhu Y, Sun Y (2009) RBX1/ROC1 disruption results in early embryonic lethality due to proliferation failure, partially rescued by simultaneous loss of p27. Proc Natl Acad Sci U S A 106:6203–6208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tetzlaff MT, Bai C, Finegold M, Wilson J, Harper JW, Mahon KA, Elledge SJ (2004a) Cyclin F disruption compromises placental development and affects normal cell cycle execution. Mol Cell Biol 24:2487–2498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tetzlaff MT, Yu W, Li M, Zhang P, Finegold M, Mahon K, Harper JW, Schwartz RJ, Elledge SJ (2004b) Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein. Proc Natl Acad Sci U S A 101:3338–3345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thalmann R, Henzl MT, Thalmann I (1997) Specific proteins of the organ of Corti. Acta Otolaryngol 117:265–268

    Article  CAS  PubMed  Google Scholar 

  • Thompson BJ, Buonamici S, Sulis ML, Palomero T, Vilimas T, Basso G, Ferrando A, Aifantis I (2007) The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J Exp Med 204:1825–1835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson BJ, Jankovic V, Gao J, Buonamici S, Vest A, Lee JM, Zavadil J, Nimer SD, Aifantis I (2008) Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7. J Exp Med 205:1395–1408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tintignac LA, Lagirand J, Batonnet S, Sirri V, Leibovitch MP, Leibovitch SA (2005) Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. J Biol Chem 280:2847–2856

    Article  CAS  PubMed  Google Scholar 

  • Tokuzawa Y, Kaiho E, Maruyama M, Takahashi K, Mitsui K, Maeda M, Niwa H, Yamanaka S (2003) Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Mol Cell Biol 23:2699–2708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsunematsu R, Nakayama K, Oike Y, Nishiyama M, Ishida N, Hatakeyama S, Bessho Y, Kageyama R, Suda T, Nakayama KI (2004) Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem 279:9417–9423

    Article  CAS  PubMed  Google Scholar 

  • Tsunematsu R, Nishiyama M, Kotoshiba S, Saiga T, Kamura T, Nakayama KI (2006) Fbxw8 is essential for Cul1-Cul7 complex formation and for placental development. Mol Cell Biol 26:6157–6169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsutsumi T, Kuwabara H, Arai T, Xiao Y, Decaprio JA (2008) Disruption of the Fbxw8 gene results in pre- and postnatal growth retardation in mice. Mol Cell Biol 28:743–751

    Article  CAS  PubMed  Google Scholar 

  • Vaites LP, Lee EK, Lian Z, Barbash O, Roy D, Wasik M, Klein-Szanto AJ, Rustgi AK, Diehl JA (2011) The Fbx4 tumor suppressor regulates cyclin D1 accumulation and prevents neoplastic transformation. Mol Cell Biol 31:4513–4523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vingill S, Brockelt D, Lancelin C, Tatenhorst L, Dontcheva G, Preisinger C, Schwedhelm-Domeyer N, Joseph S, Mitkovski M, Goebbels S et al (2016) Loss of FBXO7 (PARK15) results in reduced proteasome activity and models a parkinsonism-like phenotype in mice. EMBO J 35:2008–2025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Penfold S, Tang X, Hattori N, Riley P, Harper JW, Cross JC, Tyers M (1999) Deletion of the Cul1 gene in mice causes arrest in early embryogenesis and accumulation of cyclin E. Curr Biol 9:1191–1194

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Qiao Y, Yu J, Ren X, Wang J, Ding Y, Zhang X, Ma W, Ding Y, Liang L (2013) FBX8 acts as an invasion and metastasis suppressor and correlates with poor survival in hepatocellular carcinoma. PLoS One 8:e65495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Liu P, Inuzuka H, Wei W (2014) Roles of F-box proteins in cancer. Nat Rev Cancer 14:233–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang FF, Zhang XJ, Yan YR, Zhu XH, Yu J, Ding Y, Hu JL, Zhou WJ, Zeng ZC, Liao WT et al (2017) FBX8 is a metastasis suppressor downstream of miR-223 and targeting mTOR for degradation in colorectal carcinoma. Cancer Lett 388:85–95

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson N, Pantopoulos K (2014) The IRP/IRE system in vivo: insights from mouse models. Front Pharmacol 5:176

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Williams KL, Topp S, Yang S, Smith B, Fifita JA, Warraich ST, Zhang KY, Farrawell N, Vance C, Hu X et al (2016) CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia. Nat Commun 7:11253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson A, Murphy MJ, Oskarsson T, Kaloulis K, Bettess MD, Oser GM, Pasche AC, Knabenhans C, Macdonald HR, Trumpp A (2004) c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev 18:2747–2763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Johansen JV, Helin K (2013) Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation. Mol Cell 49:1134–1146

    Article  CAS  PubMed  Google Scholar 

  • Wu P, Wang F, Wang Y, Men H, Zhu X, He G, Ma W, Xin S, Wu J, Liao W et al (2015) Significance of FBX8 in progression of gastric cancer. Exp Mol Pathol 98:360–366

    Article  CAS  PubMed  Google Scholar 

  • Yamauchi T, Nishiyama M, Moroishi T, Kawamura A, Nakayama KI (2017) FBXL5 inactivation in mouse brain induces aberrant proliferation of neural stem progenitor cells. Mol Cell Biol 37

    Google Scholar 

  • Yan J, Yan F, Li Z, Sinnott B, Cappell KM, Yu Y, Mo J, Duncan JA, Chen X, Cormier-Daire V et al (2014) The 3M complex maintains microtubule and genome integrity. Mol Cell 54:791–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao I, Takagi H, Ageta H, Kahyo T, Sato S, Hatanaka K, Fukuda Y, Chiba T, Morone N, Yuasa S et al (2007) SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell 130:943–957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao I, Takao K, Miyakawa T, Ito S, Setou M (2011) Synaptic E3 ligase SCRAPPER in contextual fear conditioning: extensive behavioral phenotyping of Scrapper heterozygote and overexpressing mutant mice. PLoS One 6:e17317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoo SH, Mohawk JA, Siepka SM, Shan Y, Huh SK, Hong HK, Kornblum I, Kumar V, Koike N, Xu M et al (2013) Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm. Cell 152:1091–1105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshida Y, Chiba T, Tokunaga F, Kawasaki H, Iwai K, Suzuki T, Ito Y, Matsuoka K, Yoshida M, Tanaka K et al (2002) E3 ubiquitin ligase that recognizes sugar chains. Nature 418:438–442

    Article  CAS  PubMed  Google Scholar 

  • Yoshida Y, Tokunaga F, Chiba T, Iwai K, Tanaka K, Tai T (2003) Fbs2 is a new member of the E3 ubiquitin ligase family that recognizes sugar chains. J Biol Chem 278:43877–43884

    Article  CAS  PubMed  Google Scholar 

  • Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E (2018) Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 15:11–20

    Article  PubMed  Google Scholar 

  • Yu ZK, Gervais JL, Zhang H (1998) Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins. Proc Natl Acad Sci U S A 95:11324–11329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu Y, Sun L, Ren N, Li Y, Rong L, Zhao G (2014) Down-expression of F box only protein 8 correlates with tumor grade and poor prognosis in human glioma. Int J Clin Exp Pathol 7:8071–8076

    PubMed  PubMed Central  Google Scholar 

  • Yumimoto K, Matsumoto M, Oyamada K, Moroishi T, Nakayama KI (2012) Comprehensive identification of substrates for F-box proteins by differential proteomics analysis. J Proteome Res 11:3175–3185

    Article  CAS  PubMed  Google Scholar 

  • Yumimoto K, Akiyoshi S, Ueo H, Sagara Y, Onoyama I, Ueo H, Ohno S, Mori M, Mimori K, Nakayama KI (2015) F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner. J Clin Invest 125:621–635

    Article  PubMed  PubMed Central  Google Scholar 

  • Zaglia T, Milan G, Ruhs A, Franzoso M, Bertaggia E, Pianca N, Carpi A, Carullo P, Pesce P, Sacerdoti D et al (2014) Atrogin-1 deficiency promotes cardiomyopathy and premature death via impaired autophagy. J Clin Invest 124:2410–2424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou W, Wei W, Sun Y (2013) Genetically engineered mouse models for functional studies of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases. Cell Res 23:599–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zindy F, Eischen CM, Randle DH, Kamijo T, Cleveland JL, Sherr CJ, Roussel MF (1998) Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev 12:2424–2433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

We thank H. Inuzuka and W. Wei for the discussion. This study was funded in part by KAKENHI grants (18H05215) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.

Author information

Authors and Affiliations

  1. Division of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Japan

    Tadashi Nakagawa & Keiko Nakayama

  2. Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Keiichi I. Nakayama

Authors
  1. Tadashi Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keiko Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keiichi I. Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Keiko Nakayama or Keiichi I. Nakayama .

Editor information

Editors and Affiliations

  1. Radiation Oncology, University of Michigan, Ann Arbor, MI, USA

    Yi Sun

  2. Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Wenyi Wei

  3. Life Science Institute, Zhejiang University, Hangzhou, China

    Jianping Jin

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Nakagawa, T., Nakayama, K., Nakayama, K.I. (2020). Knockout Mouse Models Provide Insight into the Biological Functions of CRL1 Components. In: Sun, Y., Wei, W., Jin, J. (eds) Cullin-RING Ligases and Protein Neddylation. Advances in Experimental Medicine and Biology, vol 1217. Springer, Singapore. https://doi.org/10.1007/978-981-15-1025-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation