Post-translational modification of Parkin and its research progress in cancer

Wiley - Tập 39 - Trang 1-10 - 2019
Dan Ding1,2, Xiang Ao1,2, Ying Liu1,2, Yuan-Yong Wang1,3, Hong-Ge Fa1,2, Meng-Yu Wang1,2, Yu-Qi He4, Jian-Xun Wang1,2
1School of Basic Medical Sciences, Qingdao University, Qingdao, P. R. China
2Center for Regenerative Medicine, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, P. R. China
3Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, P. R. China
4Department of Gastroenterology, The Seventh Medical Center of PLA General Hospital, Beijing, China

Tóm tắt

Clinical practice has shown that Parkin is the major causative gene found in an autosomal recessive juvenile parkinsonism (AR-JP) via Parkin mutations and that the Parkin protein is the core expression product of the Parkin gene, which itself belongs to an E3 ubiquitin ligase. Since the discovery of the Parkin gene in the late 1990s, researchers in many countries have begun extensive research on this gene and found that in addition to AR-JP, the Parkin gene is associated with many diseases, including type 2 diabetes, leprosy, Alzheimer’s, autism, and cancer. Recent studies have found that the loss or dysfunction of Parkin has a certain relationship with tumorigenesis. In general, the Parkin gene, a well-established tumor suppressor, is deficient and mutated in a variety of malignancies. Parkin overexpression inhibits tumor cell growth and promotes apoptosis. However, the functions of Parkin in tumorigenesis and its regulatory mechanisms are still not fully understood. This article describes the structure, functions, and post-translational modifications of Parkin, and summarizes the recent advances in the tumor suppressive function of Parkin and its underlying mechanisms.

Tài liệu tham khảo

Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392(6676):605. https://doi.org/10.1038/33416. Stichel CC, Augustin M, Kühn K, Zhu XR, Engels P, Ullmer C, et al. Parkin expression in the adult mouse brain. Eur J Neurosci. 2000;12(12):4181. https://doi.org/10.1046/j.1460-9568.2000.01314.x. Seirafi M, Kozlov G, Gehring K. Parkin structure and function. FEBS J. 2015;282(11):2076–88. https://doi.org/10.1111/febs.13249. Cesari R, Martin ES, Calin GA, Pentimalli F, Bichi R, Mcadams H, et al. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc Natl Acad Sci USA. 2003;100(10):5956. https://doi.org/10.1073/pnas.0931262100. Liu J, Zhang C, Hu W, Feng Z. Parkinson’s disease-associated protein Parkin: an unusual player in cancer. Cancer Commun. 2018;38(1):40. https://doi.org/10.1186/s40880-018-0314-z. Xiang RL, Huang Y, Zhang Y, Cong X, Zhang ZJ, Wu LL, et al. Type 2 diabetes-induced hyposalivation of the submandibular gland through PINK1/Parkin-mediated mitophagy. J Cell Physiol. 2020;235(1):232–44. https://doi.org/10.1002/jcp.28962. Chakraborty J, Basso V, Ziviani E. Post translational modification of Parkin. Biol Direct. 2017;12(1):6. https://doi.org/10.1186/s13062-017-0176-3. Zhang Y, Gao J, Huang H, Dawson VL, Dawson TM. Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci USA. 2000;97(24):13354–9. https://doi.org/10.1073/pnas.240347797. Zarate-Lagunes M, Gu WJ, Blanchard V, Francois C, Muriel MP, Mouatt-Prigent A, et al. Parkin immunoreactivity in the brain of human and non-human primates: an immunohistochemical analysis in normal conditions and in Parkinsonian syndromes. J Comp Neurol. 2001;432(2):184–96. https://doi.org/10.1002/cne.1096. Shridhar V, Staub J, Huntley B, Cliby W, Jenkins R, Pass HI, et al. A novel region of deletion on chromosome 6q23.3 spanning less than 500 Kb in high grade invasive epithelial ovarian cancer. Oncogene. 1999;18(26):3913. https://doi.org/10.1038/sj.onc.1202756. Yeo CW, Ng FS, Chai C, Tan JM, Koh GR, Chong YK, et al. Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival. Can Res. 2012;72(10):2543. https://doi.org/10.1158/0008-5472.CAN-11-3060. Randow F, Youle RJ. Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe. 2014;15(4):403–11. https://doi.org/10.1016/j.chom.2014.03.012. Yorimitsu T, Klionsky DJ. Autophagy: molecular machinery for self-eating. Cell Death Differ. 2005;2(12 Suppl):1542–52. https://doi.org/10.1038/sj.cdd.4401765. Vivesbauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA. 2010;107(2):378–83. https://doi.org/10.1073/pnas.0911187107. Seok Min J, Youle RJ. PINK1- and Parkin-mediated mitophagy at a glance. J Cell Sci. 2012;125(4):795–9. https://doi.org/10.1242/jcs.093849. Kahori SF, Tsuyoshi I, Nobutaka H, Yuzuru I. PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila. PLoS Genet. 2014;10(6):e1004391. https://doi.org/10.1371/journal.pgen.1004391. Hang L, Thundyil J, Lim KL. Mitochondrial dysfunction and Parkinson disease: a Parkin-AMPK alliance in neuroprotection. Ann N Y Acad Sci. 2015;1350(1):37–47. https://doi.org/10.1111/nyas.12820. Fatima Zahra C, Stéphanie SP, Jaclyn Nicole LG, Annick F, Régis DM, Gilles D, et al. GABARAPL1 (GEC1) associates with autophagic vesicles. Autophagy. 2010;6(4):495–505. https://doi.org/10.4161/auto.6.4.11819. Youngil L, Hwa-Youn L, Hanna RA, Gustafsson ÅB. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2011;301(5):1924–31. https://doi.org/10.1152/ajpheart.00368.2011. Yasuko K, Yuzuru I, Kentaro O, Ayane K, Toshio I, Mariko S, et al. Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. Hum Mol Genet. 2007. https://doi.org/10.1093/hmg/ddl439. Ayako Y, Arno F, Yuzuru I, Ryosuke T, Kahle PJ, Christian H. Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity. J Biol Chem. 2005;280(5):3390. https://doi.org/10.1074/jbc.M407724200. Berndsen C, Wolberger C. New insights into ubiquitin E3 ligase mechanism. Nat Struct Mol Biol. 2014;21(4):301–7. https://doi.org/10.1038/nsmb.2780. Liu Y, Ao X, Ding W, Ponnusamy M, Wu W, Hao X, et al. Critical role of FOXO3a in carcinogenesis. Mol Cancer. 2018. https://doi.org/10.1186/s12943-018-0856-3. Wang X, Wang X, Hu S, Hu S, Liu L, Liu L. Phosphorylation and acetylation modifications of FOXO3a: independently or synergistically? Oncol Lett. 2017;13(5):2867–72. https://doi.org/10.3892/ol.2017.5851. Sanphui P, Biswas SC. FoxO3a is activated and executes neuron death via Bim in response to β-amyloid. Cell Death Dis. 2013;4(5):e625. https://doi.org/10.1038/cddis.2013.148. Daitoku H, Sakamaki JI, Fukamizu A. Regulation of FoxO transcription factors by acetylation and protein–protein interactions. Biochim Biophys Acta. 2011;1813(11):1954–60. https://doi.org/10.1016/j.bbamcr.2011.03.001. Yang XJ. Multisite protein modification and intramolecular signaling. Oncogene. 2005;24(10):1653–62. https://doi.org/10.1038/sj.onc.1208173. Gupta A, Anjomani-Virmouni S, Koundouros N, Dimitriadi M, Choo-Wing R, Valle A, et al. PARK2 depletion connects energy and oxidative stress to PI3K/Akt activation via PTEN S-nitrosylation. Mol Cell. 2017;65(6):999. https://doi.org/10.1016/j.molcel.2017.02.019. Avraham E, Rott R, Liani E, Szargel R, Engelender S. Phosphorylation of Parkin by the cyclin-dependent kinase 5 at the linker region modulates its ubiquitin-ligase activity and aggregation. J Biol Chem. 2007;282(17):12842. https://doi.org/10.1074/jbc.M608243200. Finnberg N, El-Deiry WS. Activating FOXO3a, NF-kappaB and p53 by targeting IKKs: an effective multi-faceted targeting of the tumor-cell phenotype? Cancer Biol Ther. 2004;3(7):614–6. https://doi.org/10.4161/cbt.3.7.1057. Sha D, Chin LS, Li L. Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-κB signaling. Hum Mol Genet. 2010;19(2):352–63. https://doi.org/10.1093/hmg/ddp501. Kim Y, Park J, Kim S, Song S, Kwon SK, Lee SH, et al. PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem Biophys Res Commun. 2008;377(3):975–80. https://doi.org/10.1016/j.bbrc.2008.10.104. Kondapalli C, Kazlauskaite A, Zhang N, Woodroof HI, Campbell DG, Gourlay R, et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2012;2(5):120080. https://doi.org/10.1098/rsob.120080. Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, et al. PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep. 2012;2(12):1002. https://doi.org/10.1038/srep01002. Poole AC, Thomas RE, Andrews LA, Mcbride HM, Whitworth AJ, Pallanck LJ. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci USA. 2008;105(5):1638–43. https://doi.org/10.1073/pnas.0709336105. Kazlauskaite A, Martínez-Torres RJ, Wilkie S, Kumar A, Peltier J, Gonzalez A, et al. Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation. EMBO Rep. 2015;16(8):939–54. https://doi.org/10.15252/embr.201540352. Chen Y, Ii GWD. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science. 2013;340(6131):471–5. https://doi.org/10.1126/science.1231031. Pinto MJ, Pedro JR, Costa RO, Almeida RD. Visualizing K48 ubiquitination during presynaptic formation by ubiquitination-induced fluorescence complementation (UiFC). Front Mol Neurosci. 2016;9:43. https://doi.org/10.3389/fnmol.2016.00043. Durcan TM, Fon EA. Mutant ataxin-3 promotes the autophagic degradation of parkin. Autophagy. 2011;7(2):233–4. https://doi.org/10.4161/auto.7.2.14224. Durcan TM, Kontogiannea M, Thorarinsdottir T, Fallon L, Williams AJ, Djarmati A, et al. The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability. Hum Mol Genet. 2011;20(1):141. https://doi.org/10.1093/hmg/ddq452. Durcan TM, Kontogiannea M, Bedard N, Wing SS, Fon EA. Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin-conjugating enzyme. J Biol Chem. 2012;287(1):531–41. https://doi.org/10.1074/jbc.M111.288449. Varshavsky A. The ubiquitin system. Nat Med. 1998;67(67):1–17. https://doi.org/10.1146/annurev.biochem.67.1.425. Hegde AN. The ubiquitin-proteasome pathway and synaptic plasticity. Learn Mem. 2010;17(7):314. https://doi.org/10.1101/lm.1504010. Federica M, Mark VDM, Suzan VDL, Domenico G. Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation. Mol Neurodegener. 2011;6(1):34. Nagy V, Dikic I. Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity. Biol Chem. 2010;391(2/3):163–9. https://doi.org/10.1515/bc.2010.021. Müller S, Hoege C, Pyrowolakis G, Jentsch S. SUMO, ubiquitin’s mysterious cousin. Nat Rev Mol Cell Biol. 2001;2(3):202–10. https://doi.org/10.1038/35056591. Hay RT. Protein modification by SUMO. Trends Biochem Sci. 2001;26(5):332–3. https://doi.org/10.1016/S0968-0004(01)01849-7. Won UJ, Kwang Chul C. Functional modulation of parkin through physical interaction with SUMO-1. J Neurosci Res. 2010;84(7):1543–54. https://doi.org/10.1002/jnr.21041. Guerra de Souza AC, Prediger RD, Cimarosti H. SUMO-regulated mitochondrial function in Parkinson’s disease. J Neurochem. 2016;137(5):673–86. https://doi.org/10.1111/jnc.13599. Watson IR, Irwin MS. Ubiquitin and ubiquitin-like modifications of the p53 family. Neoplasia. 2006;8(8):655–66. https://doi.org/10.1593/neo.06439. Bartosz W, Alicja Z, Maura W, Ted H, Maciej Z. MDM2 chaperones the p53 tumor suppressor. J Biol Chem. 2007;282(45):32603–12. https://doi.org/10.1074/jbc.M702767200. Junsoo P, Kwangsoo K, Eun-Ju L, Yun-Jee S, Si-Nae L, Kyoungsook P, et al. Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis. Proc Natl Acad Sci USA. 2007;104(43):17028–33. https://doi.org/10.1073/pnas.0609852104. Dil KA, Kito K, Abe Y, Shin RW, Kamitani T, Ueda N. NEDD8 protein is involved in ubiquitinated inclusion bodies. J Pathol. 2003;199(2):259–66. https://doi.org/10.1002/path.1283. Ji WU, Han KA, Im E, Oh Y, Lee K, Chung KC. Neddylation positively regulates the ubiquitin E3 ligase activity of parkin. J Neurosci Res. 2012;90(5):1030–42. https://doi.org/10.1002/jnr.22828. Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Sharmila A, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009;458(7239):732–6. https://doi.org/10.1038/nature07884. Yongchao Z, Morgan MA, Yi S. Targeting neddylation pathways to inactivate cullin-RING ligases for anticancer therapy. Antioxid Redox Signal. 2014;21(17):2383–400. https://doi.org/10.1089/ars.2013.5795. Choo YS, Vogler G, Wang D, Kalvakuri S, Iliuk A, Tao WA, et al. Regulation of parkin and PINK1 by neddylation. Hum Mol Genet. 2012;21(11):2514–23. https://doi.org/10.1093/hmg/dds070. Chung KK, Thomas B, Li X, Pletnikova O, Troncoso JC, Marsh L, Dawson VL, et al. S-nitrosylation of Parkin regulates ubiquitination and compromises Parkin’s protective function. Science. 2004;304(5675):1328–31. https://doi.org/10.1126/science.1093891. Cho DH, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z, et al. S-nitrosylation of Drp1 mediates β-amyloid-related mitochondrial fission and neuronal injury. Science. 2009;324(5923):102–5. https://doi.org/10.1126/science.1171091. Selvaraju V, Taylor BS, Shasha M, Fang F, Emrullah Y, Igor V, et al. Somatic mutations of the Parkinson’s disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet. 2010;42(1):77–82. https://doi.org/10.1038/ng.491. Hristova VA, Beasley SA, Rylett RJ, Shaw GS. Identification of a novel Zn2+-binding domain in the autosomal recessive juvenile Parkinson-related E3 ligase parkin. J Biol Chem. 2009;284(22):14978. https://doi.org/10.1074/jbc.m808700200. Ozawa K, Komatsubara AT, Nishimura Y, Sawada T, Kawafune H, Tsumoto H, et al. S-nitrosylation regulates mitochondrial quality control via activation of parkin. Sci Rep. 2013;3(29):2202. https://doi.org/10.1038/srep02202. Wahabi K, Perwez A, Rizvi MA. Parkin in Parkinson’s disease and cancer: a double-edged sword. Mol Neurobiol. 2018;55(8):6788–800. https://doi.org/10.1007/s12035-018-0879-1. Denison SR, Fang W, Becker NA, Birgitt S, Norman K, Phillips LA, et al. Alterations in the common fragile site gene Parkin in ovarian and other cancers. Oncogene. 2003;22(51):8370. https://doi.org/10.1038/sj.onc.1207072. Liu J, Zhang C, Zhao Y, Yue X, Wu H, Huang S, et al. Parkin targets HIF-1alpha for ubiquitination and degradation to inhibit breast tumor progression. Nat Commun. 2017;8(1):1823. https://doi.org/10.1038/s41467-017-01947-w. Stichel CC, Augustin M, Kühn K, Zhu XR, Engels P, Ullmer C, et al. Parkin expression in the adult mouse brain. Eur J Neurosci. 2010;12(12):4181–94. Lee SB, She J, Bo D, Kim JJ, Andrade MD, Jie N, et al. Multiple-level validation identifies PARK2 in the development of lung cancer and chronic obstructive pulmonary disease. Oncotarget. 2016;7(28):44211–23. https://doi.org/10.18632/oncotarget.9954. Xiaodong S, Min L, Jihui H, Dengwen L, Youguang L, Xiuchao W, et al. Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation. Cell Cycle. 2013;12(7):1133–41. https://doi.org/10.4161/cc.24215. Carroll R, Hollville E, Martin S. Parkin sensitizes toward apoptosis induced by mitochondrial depolarization through promoting degradation of Mcl-1. Cell Rep. 2014;9(4):1538–53. https://doi.org/10.1016/j.celrep.2014.10.046. Wang H, Liu B, Zhang C, Peng G, Liu M, Li D, Gu F, et al. Parkin regulates paclitaxel sensitivity in breast cancer via a microtubule-dependent mechanism. J Pathol. 2010;218(1):76–85. https://doi.org/10.1002/path.2512. Ikeuchi K, Hfujiwara M. Attenuation of proteolysis-mediated cyclin E regulation by alternatively spliced Parkin in human colorectal cancers. Int J Cancer. 2010;125(9):2029–35. https://doi.org/10.1002/ijc.24565. He S, Yang S, Niu M, Zhong Y, Dan G, Zhang Y, et al. HMG-box transcription factor 1: a positive regulator of the G1/S transition through the Cyclin-CDK-CDKI molecular network in nasopharyngeal carcinoma. Cell Death Dis. 2018;9(2):100. https://doi.org/10.1038/s41419-017-0175-4. Tay SP, Yeo CC, Chua PJ, Tan HM, Ang AX, Yip DL, et al. Parkin enhances the expression of cyclin-dependent kinase 6 and negatively regulates the proliferation of breast cancer cells. J Biol Chem. 2010;285(38):29231. https://doi.org/10.1074/jbc.M110.108241. Lee SB, Kim JJ, et al. Parkin regulates mitosis and genomic stability through Cdc20/Cdh1. Mol Cell. 2015;60(1):21–34. https://doi.org/10.1016/j.molcel.2015.08.011. Steeg PS. Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer. 2003;3(1):55. https://doi.org/10.1038/nrc967. Kaverina I, Straube A. Regulation of cell migration by dynamic microtubules. Semin Cell Dev Biol. 2011;22(9):968–74. https://doi.org/10.1016/j.semcdb.2011.09.017. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010. https://doi.org/10.1002/ijc.25516. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182. https://doi.org/10.1056/NEJM197111182852108. Rs K, Ba K. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer. 2004;4(6):423. https://doi.org/10.1038/nrc1369. Alitalo K, Carmeliet P. Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell. 2002;1(3):219–27. https://doi.org/10.1016/s1535-6108(02)00051-x. Philip M, Rowley DA, Schreiber H. Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol. 2004;14(6):433–9. https://doi.org/10.1016/j.semcancer.2004.06.006. Mitsutoshi K, Hiroki Y, Hideki K, Takashi W, Wade PA, Eling TE. DNA methylation-mediated silencing of nonsteroidal anti-inflammatory drug-activated gene (NAG-1/GDF15) in glioma cell lines. Int J Cancer. 2011;130(2):267–77. https://doi.org/10.1002/ijc.26082. Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer. 2010;121(11):2373–80. https://doi.org/10.1002/ijc.23173. Danesh J, Kaptoge S, Mann AG, Sarwar N, Wood A, Angleman SB, et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med. 2008;5(4):e78. https://doi.org/10.1371/journal.pmed.0050078. Popa C, Netea MG, van Riel PL, Jw VDM, Stalenhoef AF. The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res. 2007;48(4):751–62. https://doi.org/10.1194/jlr.R600021-JLR200. Rom O, Avezov K, Aizenbud D, Reznick AZ. Cigarette smoking and inflammation revisited. Respir Physiol Neurobiol. 2013;187(1):5–10. https://doi.org/10.1016/j.resp.2013.01.013. Freedman DM, Pfeiffer RM. Factors in association between parkinson disease and risk of cancer in Taiwan. JAMA Oncol. 2016;2(1):144. https://doi.org/10.1001/jamaoncol.2015.4151.