Skip to main content
SpringerLink
Log in

Palmitoylation as a Signal for Delivery

  • Chapter
  • First Online:
Regulation of Cancer Immune Checkpoints

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1248))

Abstract

The ligands and receptors in immune checkpoint signaling are typically transmembrane proteins, which may be regulated by palmitoylation as a reversible lipid modification. Our recent work demonstrated that palmitoylation reduces the lysosomal degradation of PD-L1 trafficking and may present a new therapeutic target. To facilitate future investigations on palmitoylation and immune checkpoints, here we summarize the molecular roles of palmitoylation on protein stability, trafficking, membrane association, and protein—protein interaction. The biological effects of palmitoylation are exemplified by well-studied substrates such as Ras, EGFR, and Wnt proteins. Finally, the strategies for targeting protein palmitoylation are discussed to facilitate future translational studies.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

References

  • Acconcia F, Ascenzi P, Fabozzi G, Visca P, Marino M (2004) S-palmitoylation modulates human estrogen receptor-alpha functions. Biochem Biophys Res Commun 316(3):878–883 PubMed PMID: 15033483

    Article  CAS  Google Scholar 

  • Adams MN, Christensen ME, He Y, Waterhouse NJ, Hooper JD (2011) The role of palmitoylation in signaling, cellular trafficking and plasma membrane localization of protease-activated receptor-2. PloS One 6(11):e28018. PubMed PMID: 22140500. Pubmed Central PMCID: PMC3226677. Epub 2011/12/06.eng

    Google Scholar 

  • Adams MN, Harrington BS, He Y, Davies CM, Wallace SJ, Chetty NP et al (2015) EGF inhibits constitutive internalization and palmitoylation-dependent degradation of membrane-spanning procancer CDCP1 promoting its availability on the cell surface. Oncogene 34(11):1375–1383. PubMed PMID: 24681947. Epub 2014/04/01. eng

    Google Scholar 

  • Adibekian A, Martin BR, Chang JW, Hsu KL, Tsuboi K, Bachovchin DA et al (2012) Confirming target engagement for reversible inhibitors in vivo by kinetically tuned activity-based probes. J Am Chem Soc 134(25):10345–10348. PubMed PMID: 22690931. Pubmed Central PMCID: PMC3392194

    Google Scholar 

  • Aramsangtienchai P, Spiegelman NA, Cao J, Lin H (2017) S-Palmitoylation of junctional adhesion molecule c regulates its tight junction localization and cell migration. J Biol Chem 292(13):5325–5334. PubMed PMID: 28196865. Pubmed Central PMCID: PMC5392678. Epub 2017/02/16. eng

    Google Scholar 

  • Arcaro A, Gregoire C, Boucheron N, Stotz S, Palmer E, Malissen B et al (2000) Essential role of CD8 palmitoylation in CD8 coreceptor function. J Immunol (Baltimore, Md: 1950) 165(4):2068–2076. PubMed PMID: 10925291

    Google Scholar 

  • Ba Q, Zhou N, Duan J, Chen T, Hao M, Yang X et al (2012) Dihydroartemisinin exerts its anticancer activity through depleting cellular iron via transferrin receptor-1. PloS One 7(8):e42703. PubMed PMID: 22900042. Pubmed Central PMCID: PMC3416848. Epub 2012/08/18. eng

    Google Scholar 

  • Babina IS, McSherry EA, Donatello S, Hill AD, Hopkins AM (2014) A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44. Breast Cancer Res BCR 6(1):R19. PubMed PMID: 24512624. Pubmed Central PMCID: PMC3978828. Epub 2014/02/12. eng

    Google Scholar 

  • Balamuth F, Brogdon JL, Bottomly K (2004) CD4 raft association and signaling regulate molecular clustering at the immunological synapse site. J Immunol (Baltimore, Md: 1950) 172(10):5887–5892. PubMed PMID: 15128768. Epub 2004/05/07. eng

    Google Scholar 

  • Bollu LR, Ren J, Blessing AM, Katreddy RR, Gao G, Xu L et al (2014) Involvement of de novo synthesized palmitate and mitochondrial EGFR in EGF induced mitochondrial fusion of cancer cells. Cell Cycle (Georgetown, Tex) 13(15):2415–2430. PubMed PMID: 25483192. Pubmed Central PMCID: PMC4128886. Epub 2014/12/09. eng

    Google Scholar 

  • Bollu LR, Katreddy RR, Blessing AM, Pham N, Zheng B, Wu X et al (2015) Intracellular activation of EGFR by fatty acid synthase dependent palmitoylation. Oncotarget 6(33):34992–35003. PubMed PMID: 26378037. Pubmed Central PMCID: PMC4741504. Epub 2015/09/18. eng

    Google Scholar 

  • Brauer PM, Tyner AL (2010) Building a better understanding of the intracellular tyrosine kinase PTK6—BRK by BRK. Biochimica et Biophysica Acta 1806(1):66–73. PubMed PMID: 20193745. Pubmed Central PMCID: PMC2885473. Epub 2010/03/03. eng

    Google Scholar 

  • Brock EJ, Ji K, Reiners JJ, Mattingly RR (2016) How to target activated Ras proteins: direct inhibition vs. induced mislocalization. Mini Rev Med Chem 16(5):358–369. PubMed PMID: 26423696. Pubmed Central PMCID: PMC4955559. Epub 2015/10/02. eng

    Google Scholar 

  • Buckley D, Duke G, Heuer TS, O’Farrell M, Wagman AS, McCulloch W et al (2017) Fatty acid synthase - Modern tumor cell biology insights into a classical oncology target. Pharmacol Ther 177:23–31. PubMed PMID: 28202364. Epub 2017/02/17. eng

    Google Scholar 

  • Butt AM, Khan IB, Hussain M, Idress M, Lu J, Tong Y (2012) Role of post translational modifications and novel crosstalk between phosphorylation and O-beta-GlcNAc modifications in human claudin-1, -3 and -4. Mol Biol Rep 39(2):1359–1369. PubMed PMID: 21617949. Epub 2011/05/28. eng

    Google Scholar 

  • Cai H, Smith DA, Memarzadeh S, Lowell CA, Cooper JA, Witte ON (2011) Differential transformation capacity of Src family kinases during the initiation of prostate cancer. Proc Natl Acad Sci USA 108(16):6579–6584. PubMed PMID: 21464326. Pubmed Central PMCID: PMC3080985. Epub 2011/04/06. eng

    Google Scholar 

  • Cao N, Li JK, Rao YQ, Liu H, Wu J, Li B et al (2016) A potential role for protein palmitoylation and zDHHC16 in DNA damage response. BMC Mol Biol 17(1):12. PubMed PMID: 27159997. Pubmed Central PMCID: PMC4862184

    Google Scholar 

  • Castellano E, Santos E (2011) Functional specificity of ras isoforms: so similar but so different. Genes Cancer 2(3):216–231. PubMed PMID: 21779495. Pubmed Central PMCID: PMC3128637

    Google Scholar 

  • Chai S, Cambronne XA, Eichhorn SW, Goodman RH (2013) MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9. Proc Natl Acad Sci USA 110(44):17898–17903. PubMed PMID: 24127608. Pubmed Central PMCID: PMC3816481

    Google Scholar 

  • Chan P, Han X, Zheng B, DeRan M, Yu J, Jarugumilli GK et al (2016) Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway. Nat Chem Biol. 12(4):282–289. PubMed PMID: 26900866. Pubmed Central PMCID: PMC4798901. Epub 2016/02/24. eng

    Google Scholar 

  • Chen B, Zheng B, DeRan M, Jarugumilli GK, Fu J, Brooks YS et al (2016) ZDHHC7-mediated S-palmitoylation of Scribble regulates cell polarity. Nat Chem Biol 12(9):686–693. PubMed PMID: 27380321. Pubmed Central PMCID: PMC4990496. Epub 2016/07/06. eng

    Google Scholar 

  • Cherukuri A, Carter RH, Brooks S, Bornmann W, Finn R, Dowd CS et al (2004) B cell signaling is regulated by induced palmitoylation of CD81. J Biol Chem 279(30):31973–31982. PubMed PMID: 15161911. Epub 2004/05/27. eng

    Google Scholar 

  • Chow A, Zhou W, Liu L, Fong MY, Champer J, Van Haute D et al (2014) Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-ĸB. Sci Rep 4:5750. PubMed PMID: 25034888. Pubmed Central PMCID: PMC4102923. Epub 2014/07/19. eng

    Google Scholar 

  • Claudinon J, Gonnord P, Beslard E, Marchetti M, Mitchell K, Boularan C et al (2009) Palmitoylation of interferon-alpha (IFN-alpha) receptor subunit IFNAR1 is required for the activation of Stat1 and Stat2 by IFN-alpha. J Biol Chem 284(36):24328–24340. PubMed PMID: 19561067. Pubmed Central PMCID: PMC2782026

    Google Scholar 

  • Coleman DT, Soung YH, Surh YJ, Cardelli JA, Chung J (2015) Curcumin prevents palmitoylation of integrin β4 in breast cancer cells. PloS One 10(5):e0125399. PubMed PMID: 25938910. Pubmed Central PMCID: PMC4418632. Epub 2015/05/06. eng

    Google Scholar 

  • Coleman DT, Gray AL, Kridel SJ, Cardelli JA (2016) Palmitoylation regulates the intracellular trafficking and stability of c-Met. Oncotarget 7(22):32664–32677. PubMed PMID: 27081699. Pubmed Central PMCID: PMC5078042. Epub 2016/04/16. eng

    Google Scholar 

  • Covey TM, Kaur S, Tan Ong T, Proffitt KD, Wu Y, Tan P et al (2012) PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation. PloS One 7(4):e34532. PubMed PMID: 22509316. Pubmed Central PMCID: PMC3324524. Epub 2012/04/18. eng

    Google Scholar 

  • Cox AD, Der CJ, Philips MR (2015) Targeting RAS membrane association: back to the future for Anti-RAS Drug discovery? Clin Cancer Res Official J Am Assoc Cancer Res 21(8):1819–1827. PubMed PMID: 25878363. Pubmed Central PMCID: PMC4400837. Epub 2015/04/17. eng

    Google Scholar 

  • Crise B, Rose JK (1992) Identification of palmitoylation sites on CD4, the human immunodeficiency virus receptor. J Biol Chem 267(19):13593–13597 PubMed PMID: 1618861

    CAS  PubMed  Google Scholar 

  • Cruz AC, Ramaswamy M, Ouyang C, Klebanoff CA, Sengupta P, Yamamoto TN et al (2016) Fas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction. Nat Commun 7:13895. PubMed PMID: 28008916. Pubmed Central PMCID: PMC5196435. Epub 2016/12/23. eng

    Google Scholar 

  • Curson JEB, Luo L, Sweet MJ, Stow JL (2018) pTRAPs: transmembrane adaptors in innate immune signaling. J Leukoc Biol. PubMed PMID: 29601097. Epub 2018/03/31. eng

    Google Scholar 

  • Davda D, El Azzouny MA, Tom CT, Hernandez JL, Majmudar JD, Kennedy RT et al (2013) Profiling targets of the irreversible palmitoylation inhibitor 2-bromopalmitate. ACS Chem Biol 8(9):1912–1917. PubMed PMID: 23844586. Pubmed Central PMCID: PMC3892994

    Google Scholar 

  • Dekker FJ, Rocks O, Vartak N, Menninger S, Hedberg C, Balamurugan R et al (2010) Small-molecule inhibition of APT1 affects Ras localization and signaling. Nat Chem Biol 6(6):449–456 PubMed PMID: 20418879

    Article  CAS  Google Scholar 

  • Dong Y, Li K, Xu Z, Ma H, Zheng J, Hu Z et al (2015) Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors. Bioorganic Med Chem 23(21):6855–6868. PubMed PMID: 26455655. Epub 2015/10/13. eng

    Google Scholar 

  • Duncan JA, Gilman AG (1998) A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS). J Biol Chem 273(25):15830–15837 PubMed PMID: 9624183

    Article  CAS  Google Scholar 

  • Fiorentino M, Zadra G, Palescandolo E, Fedele G, Bailey D, Fiore C et al (2008) Overexpression of fatty acid synthase is associated with palmitoylation of Wnt1 and cytoplasmic stabilization of beta-catenin in prostate cancer. Lab Investig J Tech Methods Pathol 88(12):1340–1348. PubMed PMID: 18838960. Pubmed Central PMCID: PMC3223737. Epub 2008/10/08. eng

    Google Scholar 

  • Fredericks GJ, Hoffmann FW, Rose AH, Osterheld HJ, Hess FM, Mercier F et al (2014) Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. Proc Natl Acad Sci USA 111(46):16478–16483. PubMed PMID: 25368151. Pubmed Central PMCID: PMC4246275. Epub 2014/11/05. eng

    Google Scholar 

  • Frohlich M, Dejanovic B, Kashkar H, Schwarz G, Nussberger S (2014) S-palmitoylation represents a novel mechanism regulating the mitochondrial targeting of BAX and initiation of apoptosis. Cell Death Dis 5:e1057. PubMed PMID: 24525733. Pubmed Central PMCID: PMC3944235. Epub 2014/02/15. eng

    Google Scholar 

  • Gajate C, Mollinedo F (2015) Lipid rafts and raft-mediated supramolecular entities in the regulation of CD95 death receptor apoptotic signaling. Apoptosis Int J Program Cell Death 20(5):584–606. PubMed PMID: 25702154. Epub 2015/02/24. eng

    Google Scholar 

  • Galluzzo P, Caiazza F, Moreno S, Marino M (2007) Role of ERbeta palmitoylation in the inhibition of human colon cancer cell proliferation. Endocr Relat Cancer 14(1):153–167 PubMed PMID: 17395984

    Article  CAS  Google Scholar 

  • Galluzzo P, Ascenzi P, Bulzomi P, Marino M (2008) The nutritional flavanone naringenin triggers antiestrogenic effects by regulating estrogen receptor alpha-palmitoylation. Endocrinology 149(5):2567–2575 PubMed PMID: 18239068

    Article  CAS  Google Scholar 

  • Garant KA, Shmulevitz M, Pan L, Daigle RM, Ahn DG, Gujar SA et al (2016) Oncolytic reovirus induces intracellular redistribution of Ras to promote apoptosis and progeny virus release. Oncogene 35(6):771–782. PubMed PMID: 25961930. Epub 2015/05/12. eng

    Google Scholar 

  • Ge L, Hoa NT, Wilson Z, Arismendi-Morillo G, Kong XT, Tajhya RB et al (2014) Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy. Int Immunopharmacol 22(2):427–443. PubMed PMID: 25027630. Pubmed Central PMCID: PMC5472047. Epub 2014/07/17. eng

    Google Scholar 

  • Gentry LR, Nishimura A, Cox AD, Martin TD, Tsygankov D, Nishida M et al (2015) Divergent roles of CAAX motif-signaled posttranslational modifications in the regulation and subcellular localization of Ral GTPases. J Biol Chem 290(37):22851–22861. PubMed PMID: 26216878. Pubmed Central PMCID: PMC4566255. Epub 2015/07/29. eng

    Google Scholar 

  • Gu W, Wang L, Wu Y, Liu JP (2018) Undo the brake of tumour immune tolerance with antibodies, peptides and small molecule compounds targeting PD-1/PD-L1 checkpoint at different locations for acceleration of cytotoxic immunity to cancer cells. Clin Exper Pharmacol Physiol. PubMed PMID: 30565707. Epub 2018/12/20. eng

    Google Scholar 

  • Guardiola-Serrano F, Rossin A, Cahuzac N, Luckerath K, Melzer I, Mailfert S et al (2010) Palmitoylation of human FasL modulates its cell death-inducing function. Cell Death Dis 1:e88. PubMed PMID: 21368861. Pubmed Central PMCID: PMC3035908. Epub 2011/03/04. eng

    Google Scholar 

  • Hancock JF, Magee AI, Childs JE, Marshall CJ (1989) All Ras proteins are polyisoprenylated but only some are palmitoylated. Cell 57(7):1167–1177 PubMed PMID: 2661017

    Article  CAS  Google Scholar 

  • Hanisch FG, Kinlough CL, Staubach S, Hughey RP (2012) MUC1 membrane trafficking: protocols for assessing biosynthetic delivery, endocytosis, recycling, and release through exosomes. Methods Molecul Biol (Clifton, NJ) 842:123–140. PubMed PMID: 22259133. Epub 2012/01/20. eng

    Google Scholar 

  • Hannoush RN (2015) Synthetic protein lipidation. Curr Opin Chem Biol 28:39–46. PubMed PMID: 26080277. Epub 2015/06/17.eng

    Google Scholar 

  • He X, Wang L, Yan J, Yuan C, Witze ES, Hua X (2016) Menin localization in cell membrane compartment. Cancer Biol Ther 17(1):114–122. PubMed PMID: 26560942. Pubmed Central PMCID: PMC4847924. Epub 2015/11/13. eng

    Google Scholar 

  • Heakal Y, Woll MP, Fox T, Seaton K, Levenson R, Kester M (2011) Neurotensin receptor-1 inducible palmitoylation is required for efficient receptor-mediated mitogenic-signaling within structured membrane microdomains. Cancer Biol Ther 12(5):427–435. PubMed PMID: 21725197. Pubmed Central PMCID: PMC3219081. Epub 2011/07/05. eng

    Google Scholar 

  • Hernandez JL, Davda D, Majmudar JD, Won SJ, Prakash A, Choi AI et al (2016) Correlated S-palmitoylation profiling of Snail-induced epithelial to mesenchymal transition. Mol BioSyst 12(6):1799–1808. PubMed PMID: 27030425. Pubmed Central PMCID: PMC5017304. Epub 2016/04/01. eng

    Google Scholar 

  • Hernandez JL, Davda D, Cheung See Kit M, Majmudar JD, Won SJ, Gang M et al (2017) APT2 Inhibition restores scribble localization and S-Palmitoylation in snail-transformed cells. Cell Chem Biol 24(1):87–97. PubMed PMID: 28065656. Pubmed Central PMCID: PMC5362123. Epub 2017/01/10. eng

    Google Scholar 

  • Heuer TS, Ventura R, Mordec K, Lai J, Fridlib M, Buckley D et al (2017) FASN inhibition and taxane treatment combine to enhance anti-tumor efficacy in diverse xenograft tumor models through disruption of tubulin palmitoylation and microtubule organization and FASN inhibition-mediated effects on oncogenic signaling and gene expression. EBioMedicine. 16:51–62. PubMed PMID: 28159572. Pubmed Central PMCID: PMC5474427. Epub 2017/02/06. eng

    Google Scholar 

  • Hobbs GA, Der CJ, Rossman KL (2016) RAS isoforms and mutations in cancer at a glance. J Cell Sci 129(7):1287–1292. PubMed PMID: 26985062. Pubmed Central PMCID: PMC4869631

    Google Scholar 

  • Ivaldi C, Martin BR, Kieffer-Jaquinod S, Chapel A, Levade T, Garin J et al (2012) Proteomic analysis of S-acylated proteins in human B cells reveals palmitoylation of the immune regulators CD20 and CD23. PloS One 7(5):e37187. PubMed PMID: 22615937. Pubmed Central PMCID: PMC3355122. Epub 2012/05/23. eng

    Google Scholar 

  • Jang D, Kwon H, Jeong K, Lee J, Pak Y (2015) Essential role of flotillin-1 palmitoylation in the intracellular localization and signaling function of IGF-1 receptor. J Cell Sci 128(11):2179–2190. PubMed PMID: 25908865. Epub 2015/04/25. eng

    Google Scholar 

  • Jeffries O, Geiger N, Rowe IC, Tian L, McClafferty H, Chen L et al (2010) Palmitoylation of the S0-S1 linker regulates cell surface expression of voltage- and calcium-activated potassium (BK) channels. J Biol Chem 285(43):33307–33314. PubMed PMID: 20693285. Pubmed Central PMCID: PMC2963414

    Google Scholar 

  • Kabouridis PS, Magee AI, Ley SC (1997) S-acylation of LCK protein tyrosine kinase is essential for its signaling function in T lymphocytes. EMBO J 16(16):4983–4998. PubMed PMID: 9305640. Pubmed Central PMCID: PMC1170133

    Google Scholar 

  • Kharbanda A, Runkle K, Wang W, Witze ES (2017) Induced sensitivity to EGFR inhibitors is mediated by palmitoylated cysteine 1025 of EGFR and requires oncogenic Kras. Biochem Biophys Res Commun 493(1):213–219. PubMed PMID: 28899783. Pubmed Central PMCID: PMC5636688. Epub 2017/09/14. eng

    Google Scholar 

  • Kinlough CL, McMahan RJ, Poland PA, Bruns JB, Harkleroad KL, Stremple RJ et al (2006) Recycling of MUC1 is dependent on its palmitoylation. J Biol Chem 281(17):12112–12122 PubMed PMID: 16507569

    Article  CAS  Google Scholar 

  • Kollmorgen G, Bossenmaier B, Niederfellner G, Haring HU, Lammers R (2012) Structural requirements for cub domain containing protein 1 (CDCP1) and Src dependent cell transformation. PloS One 7(12):e53050. PubMed PMID: 23300860. Pubmed Central PMCID: PMC3534080. Epub 2013/01/10. eng

    Google Scholar 

  • Konitsiotis AD, Chang SC, Jovanovic B, Ciepla P, Masumoto N, Palmer CP et al (2014) Attenuation of hedgehog acyltransferase-catalyzed sonic Hedgehog palmitoylation causes reduced signaling, proliferation and invasiveness of human carcinoma cells. PloS One 9(3):e89899. PubMed PMID: 24608521. Pubmed Central PMCID: PMC3946499. Epub 2014/03/13. eng

    Google Scholar 

  • Le Romancer M, Poulard C, Cohen P, Sentis S, Renoir JM, Corbo L (2011) Cracking the estrogen receptor’s posttranslational code in breast tumors. Endocr Rev 32(5):597–622. PubMed PMID: 21680538. Epub 2011/06/18. eng

    Google Scholar 

  • Liang X, Nazarian A, Erdjument-Bromage H, Bornmann W, Tempst P, Resh MD (2001) Heterogeneous fatty acylation of Src family kinases with polyunsaturated fatty acids regulates raft localization and signal transduction. J Biol Chem 276(33):30987–30994 PubMed PMID: 11423543

    Article  CAS  Google Scholar 

  • Lin DTS, Davis NG, Conibear E (2017) Targeting the Ras palmitoylation/depalmitoylation cycle in cancer. Biochem Soc Trans 45(4):913–921. PubMed PMID: 28630138. Epub 2017/06/21. eng

    Google Scholar 

  • Liu J, Pan S, Hsieh MH, Ng N, Sun F, Wang T et al (2013) Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci USA 110(50):20224–20229. PubMed PMID: 24277854. Pubmed Central PMCID: PMC3864356. Epub 2013/11/28. eng

    Google Scholar 

  • Lynes EM, Raturi A, Shenkman M, Ortiz Sandoval C, Yap MC, Wu J et al (2013) Palmitoylation is the switch that assigns calnexin to quality control or ER Ca2+ signaling. J Cell Sci 126(Pt 17):3893–3903 PubMed PMID: 23843619

    Article  CAS  Google Scholar 

  • Noland CL, Gierke S, Schnier PD, Murray J, Sandoval WN, Sagolla M et al (2016) Palmitoylation of TEAD transcription factors is required for their stability and function in Hippo pathway signaling. Structure (London, England: 1993) 24(1):179–186. PubMed PMID: 26724994. Epub 2016/01/05. eng

    Google Scholar 

  • Nussinov R, Tsai CJ, Chakrabarti M, Jang HA (2016) New view of Ras isoforms in cancers. Cancer Res 76(1):18–23. PubMed PMID: 26659836. Pubmed Central PMCID: PMC4644351. Epub 2015/12/15. eng

    Google Scholar 

  • Paige LA, Nadler MJ, Harrison ML, Cassady JM, Geahlen RL (1993) Reversible palmitoylation of the protein-tyrosine kinase p56lck. J Biol Chem 268(12):8669–8674 PubMed PMID: 8473310

    CAS  PubMed  Google Scholar 

  • Pedram A, Razandi M, Sainson RC, Kim JK, Hughes CC, Levin ER (2007) A conserved mechanism for steroid receptor translocation to the plasma membrane. J Biol Chem 282(31):22278–22288 PubMed PMID: 17535799

    Article  CAS  Google Scholar 

  • Pedram A, Razandi M, Deschenes RJ, Levin ER (2012) DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Mol Biol Cell 23(1):188–199. PubMed PMID: 22031296. Pubmed Central PMCID: PMC3248897. Epub 2011/10/28. eng

    Google Scholar 

  • Planey SL, Keay SK, Zhang CO, Zacharias DA (2009) Palmitoylation of cytoskeleton associated protein 4 by DHHC2 regulates antiproliferative factor-mediated signaling. Mol Biol Cell 20(5):1454–1463. PubMed PMID: 19144824. Pubmed Central PMCID: PMC2649263. Epub 2009/01/16. eng

    Google Scholar 

  • Polo A, Guariniello S, Colonna G, Ciliberto G, Costantini S (2016) A study on the structural features of SELK, an over-expressed protein in hepatocellular carcinoma, by molecular dynamics simulations in a lipid-water system. Mol BioSyst 12(10):3209–3222. PubMed PMID: 27524292. Epub 2016/08/16. eng

    Google Scholar 

  • Proffitt KD, Madan B, Ke Z, Pendharkar V, Ding L, Lee MA et al (2013) Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Res 73(2):502–507. PubMed PMID: 23188502. Epub 2012/11/29. eng

    Google Scholar 

  • Raturi A, Gutierrez T, Ortiz-Sandoval C, Ruangkittisakul A, Herrera-Cruz MS, Rockley JP et al (2016) TMX1 determines cancer cell metabolism as a thiol-based modulator of ER-mitochondria Ca2+ flux. J Cell Biol 214(4):433–444. PubMed PMID: 27502484. Pubmed Central PMCID: PMC4987292. Epub 2016/08/10. eng

    Google Scholar 

  • Razandi M, Pedram A, Levin ER (2010) Heat shock protein 27 is required for sex steroid receptor trafficking to and functioning at the plasma membrane. Mol Cell Biol 30(13):3249–3261. PubMed PMID: 20439495. Pubmed Central PMCID: PMC2897588. Epub 2010/05/05. eng

    Google Scholar 

  • Rebecca VW, Nicastri MC, McLaughlin N, Fennelly C, McAfee Q, Ronghe A et al (2017) A unified approach to targeting the lysosome’s degradative and growth signaling roles. Cancer Discov 7(11):1266–1283. PubMed PMID: 28899863. Pubmed Central PMCID: PMC5833978. Epub 2017/09/14. eng

    Google Scholar 

  • Resh MD (2006) Palmitoylation of ligands, receptors, and intracellular signaling molecules. Science’s STKE: signal transduction knowledge environment. 2006(359):re14. PubMed PMID: 17077383. Epub 2006/11/02. eng

    Google Scholar 

  • Roth AF, Feng Y, Chen L, Davis NG (2002) The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. J Cell Biol 159(1):23–28. PubMed PMID: 12370247. Pubmed Central PMCID: PMC2173492

    Google Scholar 

  • Runkle KB, Kharbanda A, Stypulkowski E, Cao XJ, Wang W, Garcia BA et al (2016) Inhibition of DHHC20-mediated EGFR palmitoylation creates a dependence on EGFR signaling. Mol Cell 62(3):385–96. PubMed PMID: 27153536. Pubmed Central PMCID: PMC4860254. Epub 2016/05/08. eng

    Google Scholar 

  • Santonico E, Belleudi F, Panni S, Torrisi MR, Cesareni G, Castagnoli L (2010) Multiple modification and protein interaction signals drive the Ring finger protein 11 (RNF11) E3 ligase to the endosomal compartment. Oncogene 29(41):5604–5618. PubMed PMID: 20676133. Epub 2010/08/03. eng

    Google Scholar 

  • Scheffer KD, Gawlitza A, Spoden GA, Zhang XA, Lambert C, Berditchevski F et al (2013) Tetraspanin CD151 mediates papillomavirus type 16 endocytosis. J Virol 87(6):3435–3446. PubMed PMID: 23302890. Pubmed Central PMCID: PMC3592167. Epub 2013/01/11. eng

    Google Scholar 

  • Schwab RHM, Amin N, Flanagan DJ, Johanson TM, Phesse TJ, Vincan E (2018) Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells. Dev Dyn Offic Publ Am Assoc Anat 247(3):521–530. PubMed PMID: 28560804. Epub 2017/06/01. eng

    Google Scholar 

  • Shah SM, Goel PN, Jain AS, Pathak PO, Padhye SG, Govindarajan S et al (2014) Liposomes for targeting hepatocellular carcinoma: use of conjugated arabinogalactan as targeting ligand. Int J Pharm 477(1–2):128–139. PubMed PMID: 25311181. Epub 2014/10/15. eng

    Google Scholar 

  • Sharma C, Rabinovitz I, Hemler ME (2012) Palmitoylation by DHHC3 is critical for the function, expression, and stability of integrin α6β4. Cell Mol life Sci CMLS 69(13):2233–2244. PubMed PMID: 22314500. Pubmed Central PMCID: PMC3406256. Epub 2012/02/09. eng

    Google Scholar 

  • Shenoy-Scaria AM, Gauen LK, Kwong J, Shaw AS, Lublin DM (1993) Palmitylation of an amino-terminal cysteine motif of protein tyrosine kinases p 56lck and p59fyn mediates interaction with glycosyl-phosphatidylinositol-anchored proteins. Mol Cell Biol 13(10):6385–6392. PubMed PMID: 8413237. Pubmed Central PMCID: PMC364697

    Google Scholar 

  • Shenoy-Scaria AM, Dietzen DJ, Kwong J, Link DC, Lublin DM (1994) Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae. J Cell Biol 126(2):353–363. PubMed PMID: 7518463. Pubmed Central PMCID: PMC2200018

    Google Scholar 

  • Shi Y, Bai J, Guo S, Wang J (2018) Wntless is highly expressed in advanced-stage intrahepatic cholangiocarcinoma. Tohoku J Exper Med 244(3):195–199. PubMed PMID: 29526886. Epub 2018/03/13. eng

    Google Scholar 

  • Soltysik K, Czekaj P (2015) ERalpha36–another piece of the estrogen puzzle. Eur J Cell Biol 94(12):611–625. PubMed PMID: 26522827. Epub 2015/11/03. eng

    Google Scholar 

  • Song RX, Barnes CJ, Zhang Z, Bao Y, Kumar R, Santen RJ (2004) The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor alpha to the plasma membrane. Proc Natl Acad Sci USA 101(7):2076–81. PubMed PMID: 14764897. Pubmed Central PMCID: PMC357054

    Google Scholar 

  • Tamanoi F, Lu J (2013) Recent progress in developing small molecule inhibitors designed to interfere with Ras membrane association: toward inhibiting K-Ras and N-Ras functions. Enzymes 34 Pt. B:181–200. PubMed PMID: 25034105

    Google Scholar 

  • Timson Gauen LK, Linder ME, Shaw AS (1996) Multiple features of the p 59fyn src homology 4 domain define a motif for immune-receptor tyrosine-based activation motif (ITAM) binding and for plasma membrane localization. J Cell Biol 133(5):1007–1015. PubMed PMID: 8655574. Pubmed Central PMCID: PMC2120852. Epub 1996/06/01. eng

    Google Scholar 

  • Tsai FD, Lopes MS, Zhou M, Court H, Ponce O, Fiordalisi JJ et al (2015) K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif. Proc Natl Acad Sci USA 112(3):779–784. PubMed PMID: 25561545. Pubmed Central PMCID: PMC4311840. Epub 2015/01/07. eng

    Google Scholar 

  • Tukachinsky H, Petrov K, Watanabe M, Salic A (2016) Mechanism of inhibition of the tumor suppressor Patched by Sonic Hedgehog. Proc Natl Acad Sci USA 113(40):E5866-E5875. PubMed PMID: 27647915. Pubmed Central PMCID: 5056095

    Google Scholar 

  • Urban BC, Willcox N, Roberts DJ (2001) A role for CD36 in the regulation of dendritic cell function. Proc Natl Acad Sci USA 98(15):8750–8755. PubMed PMID: 11447263. Pubmed Central PMCID: PMC37507

    Google Scholar 

  • Van Itallie CM, Gambling TM, Carson JL, Anderson JM (2005) Palmitoylation of claudins is required for efficient tight-junction localization. J Cell Sci 118(Pt 7):1427–1436 PubMed PMID: 15769849

    Article  Google Scholar 

  • van’t Hof W, Resh MD (1999) Dual fatty acylation of p 59(Fyn) is required for association with the T cell receptor zeta chain through Phosphotyrosine-Src homology domain-2 interactions. J Cell Biol 145(2):377–389. PubMed PMID: 10209031. Pubmed Central PMCID: PMC2133112. Epub 1999/04/20. eng

    Google Scholar 

  • Wang CH, Shyu RY, Wu CC, Tsai TC, Wang LK, Chen ML et al (2014) Phospholipase A/Acyltransferase enzyme activity of H-rev107 inhibits the H-RAS signaling pathway. J Biomed Sci 21:36. PubMed PMID: 24884338. Pubmed Central PMCID: PMC4012743. Epub 2014/06/03. eng

    Google Scholar 

  • Wang W, Runkle KB, Terkowski SM, Ekaireb RI, Witze ES (2015) Protein depalmitoylation is induced by Wnt5a and promotes polarized cell behavior. J Biol Chem 290(25):15707–15716. PubMed PMID: 25944911. Pubmed Central PMCID: PMC4505481. Epub 2015/05/07. eng

    Google Scholar 

  • Wang H, Yao H, Li C, Liang L, Zhang Y, Shi H et al (2017) PD-L2 expression in colorectal cancer: Independent prognostic effect and targetability by deglycosylation. Oncoimmunology 6(7):e1327494. PubMed PMID: 28811964. Pubmed Central PMCID: 5543903

    Google Scholar 

  • Wange RL (2000) LAT, the linker for activation of T cells: a bridge between T cell-specific and general signaling pathways. Sci STKE: Signal Transduct Knowl Environ 2000(63):re1. PubMed PMID: 11752630. Epub 2001/12/26. eng

    Google Scholar 

  • Wolf-Ringwall AL, Winter PW, Liu J, Van Orden AK, Roess DA, Barisas BG (2011) Restricted lateral diffusion of luteinizing hormone receptors in membrane microdomains. J Biol Chem 286(34):29818–29827. PubMed PMID: 21690095. Pubmed Central PMCID: PMC3191023. Epub 2011/06/22. eng

    Google Scholar 

  • Wu M, Huang J, Zhang J, Benes C, Jiao B, Ren R (2017) N-Arachidonoyl Dopamine Inhibits NRAS neoplastic transformation by suppressing its plasma membrane translocation. Mol Cancer Ther 16(1):57–67. PubMed PMID: 27760835. Epub 2016/10/21. eng

    Google Scholar 

  • Xu Z, Li J, Wu Y, Sun Z, Luo L, Hu Z et al (2016) Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system. Eur J Med Chem 108:154–165. PubMed PMID: 26647303. Epub 2015/12/10. eng

    Google Scholar 

  • Yang X, Guo Z, Sun F, Li W, Alfano A, Shimelis H et al (2011) Novel membrane-associated androgen receptor splice variant potentiates proliferative and survival responses in prostate cancer cells. J Biol Chem 286(41):36152–36160. PubMed PMID: 21878636. Pubmed Central PMCID: PMC3195613. Epub 2011/09/01. eng

    Google Scholar 

  • Yang Y, Hsu JM, Sun L, Chan LC, Li CW, Hsu JL et al (2019) Palmitoylation stabilizes PD-L1 to promote breast tumor growth. Cell Res 29(1):83–86. PubMed PMID: 30514902. Pubmed Central PMCID: PMC6318320

    Google Scholar 

  • Yao H, Lan J, Li C, Shi H, Brosseau J-P, Wang H et al (2019) Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours. Nat Biomed Eng

    Google Scholar 

  • Yong HY, Hwang JS, Son H, Park HI, Oh ES, Kim HH et al (2011) Identification of H-Ras-specific motif for the activation of invasive signaling program in human breast epithelial cells. Neoplasia (New York, NY) 13(2):98–107. PubMed PMID: 21403836. Pubmed Central PMCID: PMC3033589. Epub 2011/03/16. eng

    Google Scholar 

  • Zevian S, Winterwood NE, Stipp CS (2011) Structure-function analysis of tetraspanin CD151 reveals distinct requirements for tumor cell behaviors mediated by α3β1 versus α6β4 integrin. J Biol Chem 286(9):7496–7506. PubMed PMID: 21193415. Pubmed Central PMCID: PMC3045005. Epub 2011/01/05. eng

    Google Scholar 

  • Zhang W, Trible RP, Samelson LE (1998) LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Immunity 9(2):239–246 PubMed PMID: 9729044

    Article  CAS  Google Scholar 

  • Zhang P, Lock LL, Cheetham AG, Cui H (2014) Enhanced cellular entry and efficacy of tat conjugates by rational design of the auxiliary segment. Mol Pharm 11(3):964–973. PubMed PMID: 24437690. Pubmed Central PMCID: PMC3993903. Epub 2014/01/21. eng

    Google Scholar 

  • Zhao H, Liu P, Zhang R, Wu M, Li D, Zhao X et al (2015) Roles of palmitoylation and the KIKK membrane-targeting motif in leukemogenesis by oncogenic KRAS4A. J Hematol Oncol 8:132. PubMed PMID: 26715448. Pubmed Central PMCID: PMC4696201. Epub 2015/12/31. eng

    Google Scholar 

  • Zhou X, Wulfsen I, Korth M, McClafferty H, Lukowski R, Shipston MJ et al (2012) Palmitoylation and membrane association of the stress axis regulated insert (STREX) controls BK channel regulation by protein kinase C. J Biol Chem 287(38):32161–71. PubMed PMID: 22843729. Pubmed Central PMCID: PMC3442546

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Yiting Wang

  2. Department of Chemistry, Institutes of Biological Sciences, Fudan University, Shanghai, 200032, China

    Haojie Lu & Caiyun Fang

  3. Institutes of Biomedical Sciences, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200032, China

    Jie Xu

Authors
  1. Yiting Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haojie Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caiyun Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jie Xu .

Editor information

Editors and Affiliations

  1. Institutes of Biomedical Sciences, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China

    Jie Xu

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

Wang, Y., Lu, H., Fang, C., Xu, J. (2020). Palmitoylation as a Signal for Delivery. In: Xu, J. (eds) Regulation of Cancer Immune Checkpoints. Advances in Experimental Medicine and Biology, vol 1248. Springer, Singapore. https://doi.org/10.1007/978-981-15-3266-5_16

Download citation

Publish with us

Policies and ethics

Search

Navigation