Krüppel样转录因子8(KLF8)的结构及功能

万伟峰, 朱继*, 方升, 籍新潮, 吕国伟

中国生物化学与分子生物学报 ›› 2011, Vol. 27 ›› Issue (4) : 305-309.

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中国生物化学与分子生物学报 ›› 2011, Vol. 27 ›› Issue (4) : 305-309.
综述

Krüppel样转录因子8(KLF8)的结构及功能

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Structure and Function of Krüppel-like factor 8(KLF8)

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摘要

Krüppel样转录因子8(Krüppel-like factor 8, KLF8)是KLFs家族中的一员.KLF8在羧基端含有3个保守的C2H2锌指结构域,用于与DNA结合. KLF8的转录受粘着斑激酶(focal adhesion kinase, FAK)、KLF1(erythroid krüppel-like factor1)、KLF3(basic Krüppel-like factor)的调控.类泛素化是KLF8翻译后主要的修饰方式. KLF8 在氨基端含有特定的PVALS/T基序,与辅助抑制因子C末端结合蛋白(C-terminal binding protein, CtBP)相互作用,抑制调节区含CACCC元件的基因表达.此外,还可以通过招募辅助激活因子p300和p300/CBP相关因子(P/CAF)辅助激活靶基因的表达. 同时, KLF8在细胞周期循环、细胞侵袭和上皮间质转化(epithelial to mesenchymal transition,EMT)、细胞致癌性转化及肿瘤发生发展中发挥作用.

Abstract

Krüppel-like factor 8(KLF8) is a member of the family of Krüppel-like transcription factors (KLFs).It shares three well-conserved C2H2 zinc finger domains on its C-terminus, which is implicated in DNA binding. The transcription of KLF8 is modulated by focal adhesion kinase(FAK), KLF1(erythroid Krüppel-like factor) and KLF3(basic Krüppel-like factor). Sumolyation is the primary post-translational modification. Through the interaction of its N-terminal PVALS/T motif with co-repressor C-terminal binding protein (C-terminal binding protein,CtBP),KLF8 inhibits the expression of genes containing CACCC element.KLT8 can also activate target gene expression by recruiting co-activators p300 and p300/CBP associated factor (P/CAF). KLF8 plays important roles in cell cycle progression, invasion, epithelial to mesenchymal transition (EMT), oncogenic transformation and cancer development.

关键词

Krüppel样转录因子8(KLF8) / 上皮间质转化(EMT) / 粘着斑激酶(FAK) / 细胞周期素D1

Key words

Krüppel-like factors 8(KLF8) / epithelial to mesenchymal transition (EMT) / focal adhesion kinase(FAK) /   / cyclin D1

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万伟峰, 朱继*, 方升, 籍新潮, 吕国伟. Krüppel样转录因子8(KLF8)的结构及功能[J]. 中国生物化学与分子生物学报, 2011, 27(4): 305-309
WAN Wei-Feng, ZHU Ji*, FANG Sheng, JI Xin-Chao, LV Guo-Wei . Structure and Function of Krüppel-like factor 8(KLF8)[J]. Chinese Journal of Biochemistry and Molecular Biology, 2011, 27(4): 305-309
中图分类号: K34   

参考文献

参考文献(References) [1]Shindo T, Manabe I, Fukushima Y, et al. Krüppellike zincfinger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling[J]. Nat Med, 2002, 8(8): 856-863 [2]Bhattacharya R, Senbanerjee S, Lin Z, et al. Inhibition of vascular permeability factor/vascular endothelial growth factor mediated angiogenesis by the Krüppellike factor KLF2[J].J Biol Chem,2005,280(32): 28848-28851 [3]Rowland BD, Bernards R, Peeper DS. The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a contextdependent oncogene[J]. Nat Cell Biol, 2005, 7(11): 1074-1082 [4]Parmar KM, Larman HB, Dai G, et al. Integration of flowdependent endothelial phenotypes by Krüppellike factor 2[J]. J Clin Invest, 2006, 116(1): 49-58 [5]SenBanerjee S, Lin Z, Atkins GB, et al. KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation[J ]. J Exp Med, 2004, 199(10): 1305-1315 [6]Gray S, Wang B, Orihuela Y, et al. Regulation of gluconeogenesis by Krüppellike factor 15[J]. Cell Metab, 2007, 5(4): 305312 [7]Feinberg MW, Cao Z, Wara AK, et al. Krüppellike factor 4 is a mediator of proinflammatory signaling in macrophages[J]. J Biol Chem, 2005, 280(46): 38247-38258 [8]Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4): 663-676 [9]van Vliet J, Turner J, Crossley M. Human Krüppellike factor 8: a CACCCbox binding protein that associated with CtBP and represses transcription[J]. Nucleic Acids Res, 2000, 28(9): 1955-1962 [10]Wang X, Zhao J. KLF8 transcription factor participates in oncogenic transformation[J]. Oncogene,2007, 26(6): 456-461 [11]Wang X, Zheng M, Liu G, et al. KrüppelLike factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion[J]. Cancer Res, 2007, 67(15): 7184-7193 [12]Song CZ, Keller K, Murata K, et al. Functional interaction between coactivators CBP/p300, PCAF, and transcription factor FKLF2[J ]. J Biol Chem, 2002, 277(9): 7029-7036 [13]Zhang W, Kadam S, Emerson BM, et al. Sitespecific acetylation by p300 or CREB binding protein regulates erythroid Krüppellike factor transcriptional activity via its interaction with the SWISNF complex[J]. Mol Cell Biol, 2001, 21(7): 2413-2422 [14]Wei H, Wang X, Gan B, et al. Sumoylation Delimits KLF8 Transcriptional Activity Associated with the Cell Cycle Regulation[J] . J Biol Chem, 2006, 281(24): 16664-16671 [15]Quadrini KJ, Bieker JJ. Krüppellike zinc fingers bind to nuclear import proteins and are required for efficient nuclear localization of erythroid Krüppellike factor[J]. J Biol Chem, 2002, 277(35): 32243-32252 [16]Mehta TS, Lu H, Wang X, et al. A unique sequence in the N terminal regulatory region controls the nuclear localization of KLF8 by cooperating with the Cterminal zincfingers[J].Cell Res,2009, 19 (9):1098-1109 [17]Rodriguez E, Martignetti J A. The Krüppel traffic report: Cooperative signals direct KLF8 nuclear transport[J].Cell Res, 2009,19(9):1041-1043 [18]Eaton SA, Funnell AP, Sue N, et al. A network of Krüppellike factors (Klfs). Klf8 is repressed by Klf3 and activated by Klf1 in vivo [J]. J Biol Chem, 2008, 283(40):26937-26947 [19]Zhao J, Bian ZC, Yee K, et al. Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression[J].Mol Cell,2003,11(6):1503-1515 [20]Wang X, Urvalek AM, Liu J, et al. Activation of KLF8 transcription by focal adhesion kinase in human ovarian epithelial and cancer cells[J]. J Biol Chem, 2008, 283(20): 13934-13942 [21]Fu WJ, Li JC, Wu XY, et al. Small interference RNA targeting Krüppellike factor 8 inhibits the renal carcinoma 7860 cells growth in vitro and in vivo[J]. J Cancer Res Clin Oncol, 2010, 136(8):1255-1265 [22]Urvalek AM, Wang X, Lu H, et al. KLF8 recruits the p300 and PCAF coactivators to its amino terminal activation domain to activate transcription[J]. Cell Cycle, 2010, 9(3):601-611 [23]Evans PM, Liu C. New insights into KLF8mediated transactivation [J]. Cell Cycle, 2010, 9(4): 649-650 [24]Miranti CK, Brugge JS. Sensing the environment: a historical perspective on integrin signal transduction[J]. Nat Cell Biol, 2002, 4(4): E83-E90 [25]Nawshad A, Lagamba D, Polad A, et al. Transforming growth factor beta signaling during epithelialmesenchymal transformation: Implication for embryogenesis and tumor metastasis[J]. Cells Tissues Organs, 2005, 179(1): 11-23 [26]Thiery JP. Epithelial mesenchymal transition in tumor progression [J]. Nat Rev Cancer, 2002, 2(6): 442-454 [27]Peinado H, Portillo F, Cano A. Transcriptional regulation of cadherins during development and carcinogenesis[J]. Int J Dev Biol,2004, 48(56):365-375 [28]McLean GW, Carragher NO, Avizienyte E, et al. The role of focal adhesion kinase in cancera new therapeutic opportunity[J]. Nat Rev Cancer, 2005, 5(7):505-515 [29]Van Slambrouck S, Grijelmo C, De Wever O, et al. Activation of the FAKsrc molecular scaffolds and p130CasJNK signaling cascades by alphaintegrins during colon cancer cell invasion[J]. Int J Oncol, 2007, 31(6):1501-1508 [30]Golubovskaya VM, Kweh FA, Cance WG. Focal adhesion kinase and cancer[J]. Histol Histopathol, 2009, 24(4):503-510 [31]Li JC, Yang XR, Sun HX, et al. Upregulation of Krüppellike factor 8 promotes tumor invasion and indicates poor prognosis for hepatocellular carcinoma[J]. Gastroenterology, 2010,139(6):2146-2157
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