蛋白酶体激活因子REG<inline-formula><tex-math id="M1">\begin{document}$\gamma $\end{document}</tex-math></inline-formula>的肿瘤相关靶蛋白研究进展

陈少军; 李晓涛; 郑军华

doi:10.3969/j.issn.1000-5641.2018.02.013

蛋白酶体激活因子REG$\gamma $的肿瘤相关靶蛋白研究进展

doi: 10.3969/j.issn.1000-5641.2018.02.013

1.
同济大学附属上海市第十人民医院泌尿外科, 上海 200072
2.
华东师范大学生命医学研究所, 上海 200241

基金项目:

国家自然科学基金 81602216

详细信息

作者简介:
陈少军, 男, 博士研究生.研究方向为泌尿系统肿瘤的基础及临床研究.E-mail:urochen@163.com

通讯作者:
郑军华, 男, 教授, 研究方向为泌尿系统肿瘤的基础及临床研究.E-mail:zhengjh0471@sina.com

中图分类号: O157.5
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- 被引次数: 0
出版历程
- 收稿日期: 2017-02-20
- 刊出日期: 2018-03-25

Research progress of the target proteins by proteasome activator REG$\gamma $ in human cancers

1.
Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
2.
Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China

摘要

摘要: 蛋白酶体激活因子REG$\gamma $属于蛋白酶体激活因子REG（又名11 S）家族的成员之一，主要是通过激活20 S蛋白酶体以非泛素化和非ATP依赖的方式降解蛋白质.近年来，越来越多的研究表明，REG$\gamma $在多种肿瘤中出现了异常表达并与肿瘤的发生发展密切相关.REG$\gamma $主要是通过降解多种靶蛋白并调控相关的信号通路参与肿瘤的发生发展.本文综述了REG$\gamma $在肿瘤中发挥作用的靶蛋白，旨在进一步了解REG$\gamma $参与肿瘤发生发展的机制并揭示其作为人类多种肿瘤的诊断标志物和治疗靶点的潜在可能性.
- REG$\gamma $ /
- 肿瘤 /
- 靶蛋白
Abstract: The proteasome activator REG$\gamma $, which is a member of REG (11 S) proteasome activator family, can stimulate the proteolytic activity of the 20 S core proteasome to degrade proteins independent of ubiquitination and ATP. In recent years, more and more studies show that REG$\gamma $ is dysregulated in various human cancers and closely related to the oncogenesis and development of cancers. The potential mechanism by which REG$\gamma $ exerts its role in cancer development is degradation of various target proteins. We now review the target proteins of REG$\gamma $ in human cancers in order to further understand the mechanism by which REG$\gamma $ exerts its role in cancer development, and to uncover the potential of REG$\gamma $ to serve as a new marker for diagnosis and a novel target for treatment in human cancers.
- REG$\gamma $ /
- cancer /
- target proteins

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参考文献(50)

[1]	NIKAIDO T, SHIMADA K, SHIBATA M, et al. Cloning and nucleotide sequence of cDNA for Ki antigen, a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus[J]. Clinical and Experimental Immunology, 1990, 79(2):209-214. doi: 10.1111/j.1365-2249.1990.tb05180.x
[2]	RECHSTEINER M, REALINI C, USTRELL V. The proteasome activator 11S REG (PA28) and class Ⅰantigen presentation[J]. The Biochemical Journal, 2000, 345(1):1-15. http://www.ncbi.nlm.nih.gov/pubmed/10600633
[3]	MAO I, LIU J, LI X, et al. REGgamma, a proteasome activator and beyond?[J]. Cellular and Molecular Life Sciences:CMLS, 2008, 65(24):3971-3980. doi: 10.1007/s00018-008-8291-z
[4]	LI X, LONARD D M, JUNG S Y, et al. The SRC-3/AIB1 coactivator is degraded in a ubiquitin-and ATPindependent manner by the REGgamma proteasome[J]. Cell, 2006, 124(2):381-392. doi: 10.1016/j.cell.2005.11.037
[5]	GOLDBERG A L. Protein degradation and protection against misfolded or damaged proteins[J]. Nature, 2003, 426(6968):895-899. doi: 10.1038/nature02263
[6]	JUNG T, CATALGOL B, GRUNE T. The proteasomal system[J]. Molecular Aspects of Medicine, 2009, 30(4):191-196. doi: 10.1016/j.mam.2009.04.001
[7]	GERMAIN D. Ubiquitin-dependent and -independent mitochondrial protein quality controls:Implications in ageing and neurodegenerative diseases[J]. Molecular Microbiology, 2008, 70(6):1334-1341. doi: 10.1111/mmi.2008.70.issue-6
[8]	VOGES D, ZWICKL P, BAUMEISTER W. The 26S proteasome:A molecular machine designed for controlled proteolysis[J]. Annual Review of Biochemistry, 1999, 68:1015-1068. doi: 10.1146/annurev.biochem.68.1.1015
[9]	WILK S, CHEN W E, MAGNUSSON R P. Properties of the nuclear proteasome activator PA28gamma (REGgamma)[J]. Archives of Biochemistry and Biophysics, 2000, 383(2):265-271. doi: 10.1006/abbi.2000.2086
[10]	MURATA S, KAWAHARA H, TOHMA S, et al. Growth retardation in mice lacking the proteasome activator PA28gamma[J]. The Journal of Biological Chemistry, 1999, 274(53):38211-38215. doi: 10.1074/jbc.274.53.38211
[11]	BARTON L F, RUNNELS H A, SCHELL T D, et al. Immune defects in 28-kDa proteasome activator gammadeficient mice[J]. Journal of Immunology, 2004, 172(6):3948-3954. doi: 10.4049/jimmunol.172.6.3948
[12]	YU G, ZHAO Y, HE J, et al. Comparative analysis of REGgamma expression in mouse and human tissues[J]. Journal of Molecular Cell Biology, 2010, 2(4):192-198. doi: 10.1093/jmcb/mjq009
[13]	HE J, CUI L, ZENG Y, et al. REGgamma is associated with multiple oncogenic pathways in human cancers[J]. BMC Cancer, 2012(12):75. http://www.ncbi.nlm.nih.gov/pubmed/22361172
[14]	WANG X, TU S, TAN J, et al. REGgamma:A potential marker in breast cancer and effect on cell cycle and proliferation of breast cancer cell[J]. Medical Oncology, 2011, 28(1):31-41. doi: 10.1007/s12032-010-9546-8
[15]	CHAI F, LIANG Y, BI J, et al. High expression of REGgamma is associated with metastasis and poor prognosis of patients with breast cancer[J]. International Journal of Clinical and Experimental Pathology, 2014, 7(11):7834-7843. http://www.ncbi.nlm.nih.gov/pubmed/25550823
[16]	TIAN M, XIAOYI W, XIAOTAO L, et al. Proteasomes reactivator REGgamma enchances oncogenicity of MDAMB-231 cell line via promoting cell proliferation and inhibiting apoptosis[J]. Cellular and Molecular Biology, 2009, 55(Suppl):OL1121-1131. http://www.ncbi.nlm.nih.gov/pubmed/19656465
[17]	ZHANG M, GAN L, REN G S. REGgamma is a strong candidate for the regulation of cell cycle, proliferation and the invasion by poorly differentiated thyroid carcinoma cells[J]. Brazilian Journal of Medical and Biological Research, 2012, 45(5):459-465. doi: 10.1590/S0100-879X2012007500035
[18]	GUO J, HAO J, JIANG H, et al. Proteasome activator subunit 3 promotes pancreatic cancer growth via c-Mycglycolysis signaling axis[J]. Cancer Letters, 2017, 386:161-167. doi: 10.1016/j.canlet.2016.08.018
[19]	KONDO M, MORⅡSHI K, WADA H, et al. Upregulation of nuclear PA28gamma expression in cirrhosis and hepatocellular carcinoma[J]. Experimental and Therapeutic Medicine, 2012, 3(3):379-385. doi: 10.3892/etm.2011.415
[20]	LI L P, CHENG W B, LI H, et al. Expression of proteasome activator REGgamma in human laryngeal carcinoma and associations with tumor suppressor proteins[J]. Asian Pacific Journal of Cancer Prevention:APJCP, 2012, 13(6):2699-2703. doi: 10.7314/APJCP.2012.13.6.2699
[21]	LI J, FENG X, SUN C, et al. Associations between proteasomal activator PA28gamma and outcome of oral squamous cell carcinoma:Evidence from cohort studies and functional analyses[J]. EBioMedicine, 2015, 2(8):851-858. doi: 10.1016/j.ebiom.2015.07.004
[22]	LIAO L, KUANG S Q, YUAN Y, et al. Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1[J]. The Journal of Steroid Biochemistry and Molecular Biology, 2002, 83(1-5):3-14. doi: 10.1016/S0960-0760(02)00254-6
[23]	YAN J, TSAI S Y, TSAI M J. SRC-3/AIB1:Transcriptional coactivator in oncogenesis[J]. Acta Pharmacologica Sinica, 2006, 27(4):387-394. doi: 10.1111/aphs.2006.27.issue-4
[24]	HUANG H, WENG H, ZHOU H, et al. Attacking c-Myc:Targeted and combined therapies for cancer[J]. Current Pharmaceutical Design, 2014, 20(42):6543-6554. doi: 10.2174/1381612820666140826153203
[25]	LI S, JIANG C, PAN J, et al. Regulation of c-Myc protein stability by proteasome activator REGgamma[J]. Cell Death and Differentiation, 2015, 22(6):1000-1011. doi: 10.1038/cdd.2014.188
[26]	ZHAN T, RINDTORFF N, BOUTROS M. Wnt signaling in cancer[J]. Oncogene, 2017, 36(11):1461-1473. doi: 10.1038/onc.2016.304
[27]	STEWART D J. Wnt signaling pathway in non-small cell lung cancer[J]. Journal of The National Cancer Institute, 2014, 106(1):djt356. doi: 10.1093/jnci/djt356
[28]	SAWA M, MASUDA M, YAMADA T. Targeting the Wnt signaling pathway in colorectal cancer[J]. Expert Opinion on Therapeutic Targets, 2016, 20(4):419-429. doi: 10.1517/14728222.2016.1098619
[29]	XU Q, KRAUSE M, SAMOYLENKO A, et al. Wnt signaling in renal cell carcinoma[J]. Cancers, 2016, 8(6):57. doi: 10.3390/cancers8060057
[30]	LUO J. Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy[J]. Cancer Letters, 2009, 273(2):194-200. doi: 10.1016/j.canlet.2008.05.045
[31]	LI L, DANG Y, ZHANG J, et al. REGgamma is critical for skin carcinogenesis by modulating the Wnt/betacatenin pathway[J]. Nature Communications, 2015(6):6875. https://www.nature.com/articles/ncomms7875/metrics
[32]	STRACQUADANIO G, WANG X, WALLACE M D, et al. The importance of p53 pathway genetics in inherited and somatic cancer genomes[J]. Nature Reviews Cancer, 2016, 16(4):251-265. doi: 10.1038/nrc.2016.15
[33]	ZHANG Z, ZHANG R. Proteasome activator PA28 gamma regulates p53 by enhancing its MDM2-mediated degradation[J]. The EMBO Journal, 2008, 27(6):852-864. doi: 10.1038/emboj.2008.25
[34]	LIU J, YU G, ZHAO Y, et al. REGgamma modulates p53 activity by regulating its cellular localization[J]. Journal of Cell Science, 2010, 123(23):4076-4084. doi: 10.1242/jcs.067405
[35]	WEINBERG W C, DENNING M F. P21Waf1 control of epithelial cell cycle and cell fate[J]. Critical Reviews in Oral Biology and Medicine:An Official Publication of the American Association of Oral Biologists, 2002, 13(6):453-464. doi: 10.1177/154411130201300603
[36]	LI X, AMAZIT L, LONG W, et al. Ubiquitin-and ATP-independent proteolytic turnover of p21 by the REGgamma-proteasome pathway[J]. Molecular Cell, 2007, 26(6):831-842. doi: 10.1016/j.molcel.2007.05.028
[37]	KOBAYASHI T, WANG J, AL-AHMADIE H, et al. ARF regulates the stability of p16 protein via REGgammadependent proteasome degradation[J]. Molecular Cancer Research:MCR, 2013, 11(8):828-833. doi: 10.1158/1541-7786.MCR-13-0207
[38]	CHEN X, BARTON L F, CHI Y, et al. Ubiquitin-independent degradation of cell-cycle inhibitors by the REGgamma proteasome[J]. Molecular Cell, 2007, 26(6):843-852. doi: 10.1016/j.molcel.2007.05.022
[39]	ZHU H, KAVSAK P, ABDOLLAH S, et al. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation[J]. Nature, 1999, 400(6745):687-693. doi: 10.1038/23293
[40]	KWON A, LEE H L, WOO K M, et al. SMURF1 plays a role in EGF-induced breast cancer cell migration and invasion[J]. Molecules and Cells, 2013, 36(6):548-555. doi: 10.1007/s10059-013-0233-4
[41]	KWEI K A, SHAIN A H, BAIR R, et al. SMURF1 amplification promotes invasiveness in pancreatic cancer[J]. PloS One, 2011, 6(8):e23924. doi: 10.1371/journal.pone.0023924
[42]	WANG W, REN F, WU Q, et al. MicroRNA-497 inhibition of ovarian cancer cell migration and invasion through targeting of SMAD specific E3 ubiquitin protein ligase 1[J]. Biochemical and Biophysical Research Communications, 2014, 449(4):432-437. doi: 10.1016/j.bbrc.2014.05.053
[43]	LIU S, LAI L, ZUO Q, et al. PKA turnover by the REGgamma-proteasome modulates FoxO1 cellular activity and VEGF-induced angiogenesis[J]. Journal of Molecular and Cellular Cardiology, 2014, 72:28-38. doi: 10.1016/j.yjmcc.2014.02.007
[44]	LI L, ZHAO D, WEI H, et al. REGgamma deficiency promotes premature aging via the casein kinase 1 pathway[J]. Proceedings of The National Academy of Sciences of The United States of America, 2013, 110(27):11005-11010. doi: 10.1073/pnas.1308497110
[45]	SCHITTEK B, SINNBERG T. Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis[J]. Molecular Cancer, 2014, 13:231. doi: 10.1186/1476-4598-13-231
[46]	DONG S, JIA C, ZHANG S, et al. The REGgamma proteasome regulates hepatic lipid metabolism through inhibition of autophagy[J]. Cell Metabolism, 2013, 18(3):380-391. doi: 10.1016/j.cmet.2013.08.012
[47]	LIN L, BAEHRECKE E H. Autophagy, cell death, and cancer[J]. Molecular & Cellular Oncology, 2015, 2(3):e985913. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905302/
[48]	XU J, ZHOU L, JI L, et al. The REGgamma-proteasome forms a regulatory circuit with IkappaBvarepsilon and NFkappaB in experimental colitis[J]. Nature Communications, 2016(7):10761. http://www.ncbi.nlm.nih.gov/pubmed/26899380
[49]	KANAI K, ARAMATA S, KATAKAMI S, et al. Proteasome activator PA28 gamma stimulates degradation of GSK3-phosphorylated insulin transcription activator MAFA[J]. Journal of Molecular Endocrinology, 2011, 47(1):119-127. doi: 10.1530/JME-11-0044
[50]	MORⅡSHI K, OKABAYASHI T, NAKAI K, et al. Proteasome activator PA28gamma-dependent nuclear retention and degradation of hepatitis C virus core protein[J]. Journal of Virology, 2003, 77(19):10237-10249. doi: 10.1128/JVI.77.19.10237-10249.2003