留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码
x

泛素连接酶 Fbw7 的调控异常及在肿瘤中的作用

林靖 刘蓉 宋朝理

林靖, 刘蓉, 宋朝理. 泛素连接酶 Fbw7 的调控异常及在肿瘤中的作用[J]. 分子影像学杂志, 2017, 40(1): 76-80. doi: 10.3969/j.issn.1674-4500.2017.01.23
引用本文: 林靖, 刘蓉, 宋朝理. 泛素连接酶 Fbw7 的调控异常及在肿瘤中的作用[J]. 分子影像学杂志, 2017, 40(1): 76-80. doi: 10.3969/j.issn.1674-4500.2017.01.23
Jing LIN, Rong LIU, Chaoli SONG. Deregulation of Ubiquitin Ligase Fbw7 and its role in Tumor Progression[J]. Journal of Molecular Imaging, 2017, 40(1): 76-80. doi: 10.3969/j.issn.1674-4500.2017.01.23
Citation: Jing LIN, Rong LIU, Chaoli SONG. Deregulation of Ubiquitin Ligase Fbw7 and its role in Tumor Progression[J]. Journal of Molecular Imaging, 2017, 40(1): 76-80. doi: 10.3969/j.issn.1674-4500.2017.01.23

泛素连接酶 Fbw7 的调控异常及在肿瘤中的作用

doi: 10.3969/j.issn.1674-4500.2017.01.23
基金项目: 

国家自然科学基金 30930094

详细信息
    作者简介:

    林靖:林 靖,博士,E-mail: 37772092@qq.com

    通讯作者:

    宋朝理,Email: songcl123@163.com

Deregulation of Ubiquitin Ligase Fbw7 and its role in Tumor Progression

  • 摘要: 泛素蛋白酶系统对于维持细胞正常生理功能具有重要作用,Fbw7 是 E3 泛素连接酶的底物结合单位,参与泛素化降解与细胞增殖、分化、凋亡有关的重要分子,其调控异常在肿瘤细胞中极为常见。Fbw7 调控的底物包括一系列促癌分子和癌症相关转录因子,被认为是重要的抑癌分子。比如 Fbw7 可以通过调控 Cyclin E、c-Myc、Aurora A 减少因细胞周期异常而造成的染色体不稳,通过调控 p63、Mcl1 来影响细胞损伤修复并增加细胞凋亡,通过调控 TGFβ、mTOR 抑制肿瘤转移,再者可以通过对 Notch 和 Bcl2 家族分子的调控增加肿瘤细胞对化疗的敏感性。因此稳定 Fbw7 的表达可以抑制肿瘤表型的产生和发展,本文就 Fbw7 结构功能、突变机制,调控通路及其在肿瘤发生发展中的作用进行综述。

     

  • [1] Hershko A, Ciechanover A. The ubiquitin system[J]. Annu Rev Biochem, 1998, 67(4): 425-9. http://cn.bing.com/academic/profile?id=787161cfbd8c5c43960b5dcdbbf98659&encoded=0&v=paper_preview&mkt=zh-cn
    [2] Nakayama KI, Nakayama K. Ubiquitin ligases: cell-cycle control and cancer[J]. Nat Rev Cancer, 2006, 6(5): 369-81. doi: 10.1038/nrc1881
    [3] Lau W, Fukushima H, Wei W. The Fbw7 and betaTRCP E3 ubiquitin ligases and their roles in tumorigenesis[J]. Front Biosci,2012, 17(6): 2197-212. http://cn.bing.com/academic/profile?id=3ee47c38e0144e794bb89fa44ee0003a&encoded=0&v=paper_preview&mkt=zh-cn
    [4] Bredel M, Bredel C, Juric D, et al. Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas[J]. Cancer Res, 2005, 65(19): 8679-89. doi: 10.1158/0008-5472.CAN-05-1204
    [5] Welcker M, Clurman E. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation[J]. Nat Rev Cancer, 2008, 8(2): 83-93. doi: 10.1038/nrc2290
    [6] Wang L, Ye XT, Liu YY, et al. Aberrant regulation of FBW7 in cancer[J]. Oncotarget, 2014, 5(8): 2000-15. doi: 10.18632/oncotarget
    [7] Hao B, Oehlmann S, Sowa E, et al. Structure of a Fbw7-Skp1-cclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases[J]. Mol Cell, 2007, 26(1): 131-43. doi: 10.1016/j.molcel.2007.02.022
    [8] Welcker M, Larimore A, Swanger J, et al. Fbw7 dimerization determines the specificity and robustness of substrate degradation[J]. Genes Dev, 2013, 27(23): 2531-6. doi: 10.1101/gad.229195.113
    [9] Koepp M, Schaefer K, Ye X, et al. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase[J]. Science, 2001, 294(40): 173-7. http://cn.bing.com/academic/profile?id=bb4f99e61685127a44599d7dba5e7855&encoded=0&v=paper_preview&mkt=zh-cn
    [10] Cheng YB, Li G. Role of the ubiquitin ligase Fbw7 in Cancer progression[J]. Cancer Metastasis Rev, 2012, 31(1/2): 75-87. http://cn.bing.com/academic/profile?id=3910e0d1aa52b8c75d52c5ff7ac717e7&encoded=0&v=paper_preview&mkt=zh-cn
    [11] Akhoondi S, Lindström L, Widschwendter M, et al. Inactivation of FBXW7/hCDC4-β expression by promoter hypermethylation is associated with favorable prognosis in primary breast cancer[J]. Breast Cancer Res, 2010, 12(6): R105-8. doi: 10.1186/bcr2788
    [12] Inuzuka H, Shaik S, Onoyama I, et al. SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction[J]. Nature, 2011, 471(36): 104-9. http://d.scholar.cnki.net/detail/SJPD0711_U/SJPD12102000196395
    [13] Flügel D, Görlach A, Kietzmann T. GSK-3β regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1α[J]. Blood, 2012, 119(5): 1292-301. doi: 10.1182/blood-2011-08-375014
    [14] Pérez BB, Farràs R. Regulation of GSK3β-FBXW7-JUNB axis[J]. Oncotarget, 2013, 4(7): 956-7. doi: 10.18632/oncotarget
    [15] Ren H, Zhao LQ, Li YK, et al. The PI3 kinase inhibitor NVP-BKM120 induces GSK3/FBXW7-dependent Mcl-1 degradation, contributing to induction of apoptosis and enhancement of TRAIL-induced apoptosis[J]. Cancer Lett, 2013,338(2): 229-38. doi: 10.1016/j.canlet.2013.03.032
    [16] Mao H, Perez LJ, Wu D, et al. Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene[J]. Nature, 2004, 432(718): 775-9. http://cn.bing.com/academic/profile?id=0d2dda8a8647d3497182d54c2b018086&encoded=0&v=paper_preview&mkt=zh-cn
    [17] Kurashige J, Watanabe M, Iwatsuki M, et al. Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma[J]. Br J Cancer, 2012, 106(1): 182-8. http://cn.bing.com/academic/profile?id=72c94f5dd39659e02a9913464f4ad871&encoded=0&v=paper_preview&mkt=zh-cn
    [18] Li L, Sarver AL, Khatri R, et al. Sequential expression of miR-182 and miR-503 cooperatively targets FBXW7, contributing to the malignant transformation of colon adenoma to adenocarcinoma[J]. J Pathol, 2014, 234(4): 488-501. doi: 10.1002/path.2014.234.issue-4
    [19] Kumar V, Palermo R, Talora C, et al. Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia[J]. Leukemia, 2014, 28(12): 2324-35. doi: 10.1038/leu.2014.133
    [20] Esquejo M, Jeon TI, Osborne F. Lipid-cell cycle nexus: SREBP regulates microRNAs targeting Fbxw7[J]. Cell Cycle, 2014, 13(3):339-40. doi: 10.4161/cc.27509
    [21] Balamurugan K, Wang M, Tsai H, et al. The tumour suppressor C/ EBPδ inhibits FBXW7 expression and promotes mammary tumour metastasis[J]. EMBO J, 2010, 29(24): 4106-17. doi: 10.1038/emboj.2010.280
    [22] Min H, Lau W, Lee H, et al. Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase[J]. Mol Cell, 2012, 46(6): 771-83. doi: 10.1016/j.molcel.2012.04.012
    [23] Sancho R, Blake M, Tendeng C, et al. Fbw7 repression by hes5 creates a feedback loop that modulates Notch-mediated intestinal and neural stem cell fate decisions[J]. PLoS Biol, 2013, 11(6): e1001586-94. doi: 10.1371/journal.pbio.1001586
    [24] Ji S, Qin Y, Shi S, et al. ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer[J]. Cell Res, 2015, 25(5): 561-73. doi: 10.1038/cr.2015.30
    [25] Evans T, Rosenthal T, Youngblom J, et al. Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division[J]. Cell, 1983, 33(2): 389-96. doi: 10.1016/0092-8674(83)90420-8
    [26] Hartwell LH, Culotti J. Genetic control of the cell division cycle in yeast [J]. Science, 1974, 183(4120): 46-51. doi: 10.1126/science.183.4120.46
    [27] Spruck H, Won A, Reed I. Deregulated cyclin E induces chromosome instability[J]. Nature, 1999, 401(50): 297-300. http://cn.bing.com/academic/profile?id=23d0935935ef8eaf9495e82057660588&encoded=0&v=paper_preview&mkt=zh-cn
    [28] Minella C, Grim E, Welcker M, et al. p53 and SCFFbw7 cooperatively restrain cyclin e-associated genome instability[J]. Oncogene, 2007, 26(48): 6948-53. doi: 10.1038/sj.onc.1210518
    [29] Eilers M, Schirm S, Bishop M. The MYC protein activates transcription of the alpha-prothymosin gene[J]. EMBO J, 1991, 10(1): 133-41. http://cn.bing.com/academic/profile?id=a105ffc277c9e9ab4e715d94002356f4&encoded=0&v=paper_preview&mkt=zh-cn
    [30] Yada M, Hatakeyama S, Kamura T, et al. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7[J]. EMBO J, 2004, 23(10): 2116-25. doi: 10.1038/sj.emboj.7600217
    [31] Artavanis TA, Rand S, Lake RJ,et al.Notch signaling:cell fate control and signal integration in development[J]. Science,1999,32(284): 770–6. http://cn.bing.com/academic/profile?id=4d191757632a88ed362d946606481986&encoded=0&v=paper_preview&mkt=zh-cn
    [32] Oberg C, Li J, Pauley A, et al. The notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog[J]. J Biol Chem, 2001, 276(38): 35847-53. doi: 10.1074/jbc.M103992200
    [33] Fryer J, White B, Jones A. Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover[J]. Mol Cell, 2004, 16(4): 509-20. doi: 10.1016/j.molcel.2004.10.014
    [34] Ishikawa Y, Onoyama I, Nakayama I, et al. Notch-dependent cell cycle arrest and apoptosis in mouse embryonic fibroblasts lacking Fbxw7[J]. Oncogene, 2008, 27(47): 6164-74. doi: 10.1038/onc.2008.216
    [35] Hartl M, Bader G, Bister K. Molecular targets of the oncogenic transcription factor jun[J]. Curr Cancer Drug Targ, 2003, 3(1):41-55. doi: 10.2174/1568009033333781
    [36] Musti M, Treier M, Bohmann D. Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases[J]. Science, 1997, 275(98): 400-2. http://cn.bing.com/academic/profile?id=f271131d69d52233cfa153737a6acfcb&encoded=0&v=paper_preview&mkt=zh-cn
    [37] Wei WY, Jin JP, Schlisio S, et al. The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase[J]. Cancer Cell, 2005, 8(1): 25-33. doi: 10.1016/j.ccr.2005.06.005
    [38] Marumoto T, Zhang D, Saya H. Aurora-A - a Guardian of poles[J]. Nat Rev Cancer, 2005, 5(1): 42-50. doi: 10.1038/nrc1526
    [39] Giet R, Petretti C, kinases C.Aurora prigent,aneuploidy and cancer: a coincidence or a real Link[J]. Trends Cell Biol, 2005, 15(7):241-50. http://cn.bing.com/academic/profile?id=2af6e10fb84ccbe97fa036919f91e3c4&encoded=0&v=paper_preview&mkt=zh-cn
    [40] Kwon W, Kim J, Wu D, et al. Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development [J]. Mol Cancer Res, 2012, 10(6): 834-44. doi: 10.1158/1541-7786.MCR-12-0025
    [41] Galli F, Rossi M, D'alessandra Y, et al. MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation[J]. J Cell Sci, 2010, 123(Pt 14): 2423-33. http://cn.bing.com/academic/profile?id=0d875655fca6ed61422a4889119da98b&encoded=0&v=paper_preview&mkt=zh-cn
    [42] Massagué J, Wotton D. Transcriptional control by the TGF-beta/ Smad signaling system[J]. EMBO J, 2000, 19(8): 1745-54. doi: 10.1093/emboj/19.8.1745
    [43] Bengoechea AT, Ericsson J. Tumor suppressor Fbxw7 regulates TGFβ signaling by targeting TGIF1 for degradation[J]. Oncogene,2010, 29(38): 5322-8. doi: 10.1038/onc.2010.278
    [44] Wertz IE, Kusam S, Lam C, et al. Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7[J]. Nature,2011, 471(7336): 110-4. doi: 10.1038/nature09779
    [45] Wolfer A, Ramaswamy S. MYC and metastasis[J]. Cancer Res,2011, 71(63): 2034–7. http://cn.bing.com/academic/profile?id=d9b626eb133cfbf6ea0ff67ab4757476&encoded=0&v=paper_preview&mkt=zh-cn
    [46] Fletcher JI, Haber M, Henderson MJ. ABC transporters in cancer: more than just drug efflux pumps[J]. Nat Rev Cancer, 2010, 10(2):147-56. doi: 10.1038/nrc2789
    [47] Happold C, Roth P, Wick W, et al. Distinct molecular mechanisms of acquired resistance to temozolomide in glioblastoma cells[J]. J Neurochem, 2012, 122(2): 444-55. doi: 10.1111/jnc.2012.122.issue-2
    [48] Zhang JH, Stevens F, Laughton A, et al. Acquired resistance to temozolomide in glioma cell lines: molecular mechanisms and potential translational applications[J]. Oncology, 2010, 78(2):103-14. doi: 10.1159/000306139
    [49] Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance[J]. Nat Rev Cancer, 2005, 5(4): 275-84. doi: 10.1038/nrc1590
    [50] O'neil J, Grim J, Strack P, et al. FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors[J]. J Exp Med, 2007, 204(8): 1813-24. doi: 10.1084/jem.20070876
  • 加载中
计量
  • 文章访问数:  553
  • HTML全文浏览量:  229
  • PDF下载量:  3
  • 被引次数: 0
出版历程
  • 收稿日期:  2016-09-14
  • 刊出日期:  2017-01-01

目录

    /

    返回文章
    返回

    关于《分子影像学杂志》变更刊期通知

    各位专家、作者、读者:

    为了缩短出版时滞,促进科研成果的快速传播,我刊自2024年1月起,刊期由双月刊变更为月刊。本刊主要栏目有:基础研究、临床研究、技术方法、综述等。

    感谢各位专家、作者、读者长期以来对我刊的支持与厚爱!

    南方医科大学学报编辑部

    《分子影像学杂志》

    2023年12月27日