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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
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
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
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
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
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
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
Baguma-Nibasheka M, Kablar B (2009) Abnormal retinal development in the Btrc null mouse. Dev Dyn 238:2680–2687
Bai C, Richman R, Elledge SJ (1994) Human cyclin F. EMBO J 13:6087–6098
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
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
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
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
Boulard M, Edwards JR, Bestor TH (2016) Abnormal X chromosome inactivation and sex-specific gene dysregulation after ablation of FBXL10. Epigenetics Chromatin 9:22
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
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
Camaschella C (2015) Iron-deficiency anemia. N Engl J Med 372:1832–1843
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
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
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
Davis RJ, Welcker M, Clurman BE (2014) Tumor suppression by the Fbw7 ubiquitin ligase: mechanisms and opportunities. Cancer Cell 26:455–464
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
Deshaies RJ, Joazeiro CA (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78:399–434
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
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
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
Fleming RE, Ponka P (2012) Iron overload in human disease. N Engl J Med 366:348–359
Fodde R (2002) The APC gene in colorectal cancer. Eur J Cancer 38:867–871
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
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
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
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
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
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
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
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
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
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
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
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
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
Hentze MW, Muckenthaler MU, Galy B, Camaschella C (2010) Two to tango: regulation of Mammalian iron metabolism. Cell 142:24–38
Hinds P, Pietruska J (2017) Senescence and tumor suppression. F1000Res 6:2121
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
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
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
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
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
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
Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386:896–912
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
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
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
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
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
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
Kleiger G, Mayor T (2014) Perilous journey: a tour of the ubiquitin-proteasome system. Trends Cell Biol 24:352–359
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
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
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
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
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
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
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
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
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
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
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
Madgwick S, Jones KT (2007) How eggs arrest at metaphase II: MPF stabilisation plus APC/C inhibition equals cytostatic factor. Cell Div 2:4
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
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
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
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
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
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
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
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
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
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
Muckenthaler MU, Rivella S, Hentze MW, Galy B (2017) A red carpet for iron metabolism. Cell 168:344–361
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
Nakagawa T, Nakayama K (2015) Protein monoubiquitylation: targets and diverse functions. Genes Cells 20:543–562
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
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
Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6:369–381
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
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
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
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
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
Nita A, Nishiyama M, Muto Y, Nakayama KI (2016) FBXL12 regulates T-cell differentiation in a cell-autonomous manner. Genes Cells 21:517–524
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
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
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
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
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
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
Petroski MD, Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 6:9–20
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
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
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
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
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
Rotin D, Kumar S (2009) Physiological functions of the HECT family of ubiquitin ligases. Nat Rev Mol Cell Biol 10:398–409
Rouault TA (2013) Iron metabolism in the CNS: implications for neurodegenerative diseases. Nat Rev Neurosci 14:551–564
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
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
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
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
Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348:56–61
Shimizu K, Nihira NT, Inuzuka H, Wei W (2018) Physiological functions of FBW7 in cancer and metabolism. Cell Signal 46:15–22
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
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
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
Smit JJ, Sixma TK (2014) RBR E3-ligases at work. EMBO Rep 15:142–154
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
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
Sumida Y, Yoneda M (2018) Current and future pharmacological therapies for NAFLD/NASH. J Gastroenterol 53:362–376
Swatek KN, Komander D (2016) Ubiquitin modifications. Cell Res 26:399–422
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
Takahashi JS (2017) Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 18:164–179
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
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
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
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
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
Thalmann R, Henzl MT, Thalmann I (1997) Specific proteins of the organ of Corti. Acta Otolaryngol 117:265–268
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
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
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
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
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
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
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
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
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
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
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
Wang Z, Liu P, Inuzuka H, Wei W (2014) Roles of F-box proteins in cancer. Nat Rev Cancer 14:233–247
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
Wilkinson N, Pantopoulos K (2014) The IRP/IRE system in vivo: insights from mouse models. Front Pharmacol 5:176
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Singapore Pte Ltd.
About this chapter
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
DOI: https://doi.org/10.1007/978-981-15-1025-0_10
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-1024-3
Online ISBN: 978-981-15-1025-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)