POZ 锌指蛋白在发育和肿瘤发生中的作用

摘要/Abstract

摘要： POZ 锌指蛋白是一类在进化中高度保守的蛋白，具有多种重要的生物学功能。POZ 锌指蛋白主要作为一种转录抑制因子而存在，通过POZ 结构域招募一些转录辅阻遏物而调节靶基因的表达。近年来的研究发现，POZ 锌指蛋白在发育和肿瘤的发生中有着重要的作用，综述5 个POZ 锌指蛋白在肿瘤的发生和生物体发育中的作用及功能，为人们进一步了解POZ 锌指蛋白的功能提供资料。

关键词: POZ, 锌指蛋白, 发育, 肿瘤发生

Abstract: POZ-ZF proteins are highly conserved proteins implicated many biological processes in invertebrate and vertebrate. Members of the POZ-ZF protein contain an amino-terminal POZ domain and a carboxy-terminal DNA-binding domain made of one or more zinc finger motifs and usually act as transcriptional co-repressors to regulate target genes expression. Recent studies showed that POZ-ZF proteins play important roles in development and oncogenesis. In this review, we summarize studies of five POZ-ZF proteins, which is helpful to further understand POZ-ZF proteins.

Key words: POZ-ZF protein, Development, Oncogenesis

梅竹, 杨予涛, 徐志卿. POZ 锌指蛋白在发育和肿瘤发生中的作用[J]. 生物技术通报, 2013, 0(2): 55-60.

Mei Zhu, Yang Yutao, Xu Zhiqing. Roles of POZ-ZF Proteins in Development and Oncogenesis[J]. Biotechnology Bulletin, 2013, 0(2): 55-60.

参考文献

［1] Albagli O, Dhordain P, Deweindt C, et al. The BTB/POZ domain: a new protein-protein interaction motif common to DNA-and actinbinding proteins［J]. Cell Growth Differ, 1995, 6(3)：1193- 1198.
[2] Stogios PJ, Downs GS, Jauhal JJ, et al. Sequence and structural analysis of BTB domain proteins［J]. Genome Biol, 2005, 6:R82.
[3] Collins T, Stone JR, Williams AJ. All in the family:The BTB/POZ, KRAB, and SCAN domains［J]. Mol Cell Biol, 2001, 21:3609- 3615.
[4] David G, Alland L, Hong SH, et al. Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein［J]. Oncogene, 1998, 16: 2549-2556.
[5] Melnick A, Carlile G, Ahmad KF, et al. Critical residues within the BTB domain of PLZF and Bcl-6 modulate interaction with corepressors［J]. Mol Cell Biol, 2002, 22:1804-1818.
[6] Ahmad KF, Melnick A, Lax S, et al. Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain［J]. Mol Cell, 2003, 12: 1551-1564.
[7] Dhordain P, Lin RJ, Quief S, et al. The LAZ3(BCL-6)oncoprotein recruits a SMRT/mSIN3A/histone deacetylase containing complex to mediate transcriptional repression［J]. Nucleic Acids Res, 1998, 26:4645-4651.
[8] Huynh KD, Bardwell VJ. The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT［J]. Oncogene, 1998, 17:2473-2484.
[9] Chen Z, Brand NJ, Chen A, et al. Fusion between a novel Kruppellike zinc finger gene and the retinoic acid receptor-α locus due to a variant t(11 ；17)translocation associated with acute promyelocytic leukemia［J]. EMBO J, 1993, 12:1161-1167.
[10] Nagy L, Kao HY, Chakravarti D, et al. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histon deacetylase［J]. Cell, 1997, 89(3)：373-380.
[11] Lin RJ, Nagy L, Inoue S, et al. Role of the histone deactylase complex in acute promyelocytic leukaemia［J]. Nature, 1998, 106:811-814.
[12] Grignani F, De Matteis S, Nervi C, et al. Fusion proteins of the retinoic acid receptor-α recruit histone deacetylase in promyelocytic leukaemia［J]. Nature, 1998, 391(6669)：815-818.
[13] Alcalay M, Meani N, Gelmetti V, et al. Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair［J]. J Clin Invest, 2003, 112(11)：1751-1761.
[14] Müller C, Yang R, Park DJ, et al. The aberrant fusion proteins PMLRAR alpha and PLZF-RAR alpha contribute to the overexpression 2013年第2期59 梅竹等：POZ 锌指蛋白在发育和肿瘤发生中的作用 of cyclin A1 in acute promyelocytic leukemia［J]. Blood, 2000, 96:3894-3899.
[15] Kwok C, Zeisig BB, Dong S, So CW. Forced homo-oligomerization of RARalpha leads to transformation of primary hematopoietic cells［J]. Cancer Cell, 2006, 9:95-108.
[16] Insinga A, Monestiroli S, Ronzoni S, et al. Impairment of p53 acetylation, stability and function by an oncogenic transcription factor［J]. EMBO J, 2004, 23(5)：1144-1154.
[17] Barna M, Hawe N, Niswander L, Pandolfi PP. Plzf regulates limb and axial skeletal patterning［J]. Nat Genet, 2000, 25:166-172.
[18] Barna M, Pandolfi PP, Niswander L. Gli3 and Plzf cooperate in proximal limb patterning at early stages of limb development［J]. Nature, 2005, 436:277-281.
[19] Costoya JA, Hobbs RM, Barna M, et al. Essential role of Plzf in maintenance of spermatogonial stem cells［J]. Nat Genet, 2004, 36:653-659.
[20] Hobbs RM, Seandel M, Falciatori I, et al. Plzf regulates germline progenitor self-renewal by opposing mTORC1［J]. Cell, 2010, 142(3)：468-479.
[21] Mikkelsen TS, Xu Z, Zhang X, et al. Comparative epigenomic analysis of murine and human adipogenesis［J]. Cell, 2010, 143 (1)：156-169.
[22] Pasqualucci L, Bereschenko O, Niu H, et al. Molecular pathogenesis of non-Hodgkin’s lymphoma:the role of Bcl-6, Leuk［J]. Lymphoma, 2003, 44(suppl 3)：S5-S12.
[23] Cattoretti G, Pasqualucci L, Ballon G, et al. Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice［J]. Cancer Cell, 2005, 7:445-455.
[24] Baron BW, Anastasi J, Montag A, et al. The human BCL6 transgene promotes the development of lymphomas in the mouse［J]. Proc Natl Acad Sci USA, 2004, 101:14198-14203.
[25] Polo JM, Dell’Oso T, Ranuncolo SM, et al. Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells［J]. Nat Med, 2004, 10:1329-1335.
[26] Chattopadhyay A, Tate SA, Beswick RW, et al. A peptide aptamer to antagonize BCL-6 function［J]. Oncogene, 2006, 25:2223- 2233.
[27] Basso K, Dalla-Favera R. BCL6:master regulator of the germinal center reaction and key oncogene in B cell lymphomagenesis［J]. Adv Immunol, 2010, 105:193-210.
[28] Shaffer AL, Yu X, He Y, et al. BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control[J]. Immunity, 2000, 13:199-212.
[29] Kojima S, Hatano M, Okada S, et al. Testicular germ cell apoptosis in Bcl6-deficient mice［J]. Development, 2001, 128:57-65.
[30] Wales MM, Biel MA, EL Deiry W, et al. p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3［J]. Nat Med, 1995, 1(6)：570-577.
[31] Fujii H, Biel MA, Zhou W, et al. Methylation of the HIC-1 candidate tumor suppressor gene in human breast cancer［J]. Oncogene, 1998, 16:2159-2164.
[32] Chen WY, Zeng X, Carter MG, et al. Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors［J]. Nat Genet, 2003, 33:197-202.
[33] Chen W, Cooper TK, Zahnow CA, et al. Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in tumorigenesis［J]. Cancer Cell, 2004, 6:387-398.
[34] Chen WY, Wang DH, Yen RC, et al. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-Dependent DNA-damage responses［J]. Cell, 2005, 123(3)：437-448.
[35] Abouzeid HE, Kassem AM, Abdel Wahab AH, et al. Promoter hypermethylation of RASSF1A, MGMT, and HIC-1 genes in benign and malignant colorectal tumors［J]. Tumour Biol, 2011, 32(5)： 845-852.
[36] Carter MG, Johns MA, Zeng X, et al. Mice deficient in the candidate tumor suppressor gene Hic1 exhibit developmental defects of structures affected in the Miller-Dieker syndrome［J]. Hum Mol Genet, 2000, 9:413-419.
[37] Reynolds AB, Carnahan RH. Regulation of cadherin stability and turnover by p120ctn:implications in. disease and cancer［J]. Semin Cell Dev Biol, 2004, 15:657-663.
[38] Buck-Koehntop BA, Martinez-Yamout MA, Jane Dyson H, Wright PE. Kaiso uses all three zinc fingers and adjacent sequence motifs for high affinity binding to sequence-specific and methyl-CpG DNA targets［J]. FEBS Lett, 2012, 586(6)：734-739.
[39] Spring CM, Kelly KF, O’Kelly I, et al. The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin［J]. Exp Cell Res, 2005, 305(2)：253- 265.
[40] Lopes EC, Valls E, Figueroa ME. Kaiso contributes to DNA 生物技术通报 Biotechnology Bulletin 2013年第2期60 methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines［J]. Cancer Res, 2008, 68(18)：7258-7263.
[41] Zhang PX, Wang Y, Liu Y, et al. p120-catenin isoform 3 regulates subcellular localization of Kaiso and promotes invasion in lung cancer cells via a phosphorylation-dependent mechanism［J]. Int J Oncol, 2011, 38(6)：1625-1635.
[42] Kim SW, Park JI, Spring CM, et al. Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120- catenin［J]. Nat Cell Biol, 2004, 6(12)：1212-1220.
[43] Park JI, Kim SW, Lyons JP, et al. Kaiso/p120-catenin and TCF/ beta-catenin complexes coordinately regulate canonical Wnt gene targets［J]. Dev Cell, 2005, 8(6)：843-854.
[44] Nusse R. Wnt signaling in disease and in development［J]. Cell Res, 2005, 15:28-32.
[45] Iioka H, Doerner SK, Tamai K. Kaiso is a bimodal modulator for Wnt/beta-catenin signaling［J]. FEBS Lett, 2009, 583(4)： 627-632.
[46] Filion GJ, Zhenilo S, Salozhin S, et al. A family of human zinc finger proteins that bind methylated DNA and repress transcription［J]. Mol Cell Biol, 2006, 26:169-181.
[47] Maeda T, Hobbs RM, Merghoub T, et al. Role of the proto-oncogene pokemon in cellular transformation and ARF repression［J]. Nature, 2005, 433:278-285.
[48] Zhao ZH, Wang SF, Yu L, et al. Overexpression of Pokemonin nonsmall cell lung cancer and foreshowing tumor biological behavior as well as clinical results［J]. Lung Cancer, 2008, 62(1)：113- 119.
[49] Aggarwal A, Hunter WJ 3rd, Aggarwal H, et al. Expression of leukemia/lymphoma-related factor(LRF/POKEMON)in human breast carcinoma and other cancers［J]. Exp Mol Pathol, 2010, 89(2)：140-148.
[50] Aggarwal H, Aggarwal A, Hunter WJ 3rd, et al. Expression of leukemia/lymphoma related factor(LRF/Pokemon)in human benign prostate hyperplasia and prostate cancer［J]. Exp Mol Pathol, 2011, 90(2)：226-230.
[51] Jeon BN, Yoo JY, Choi WI, et al. Proto-oncogene FBI-1(Pokemon/ ZBTB7A)represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of corepressors[J]. J Biol Chem, 2008, 283:33199-33210.
[52] Zu X, Ma J, Liu H, et al. Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression［J]. Breast Cancer Res, 2011, 13:R26.
[53] Cui JJ, Yang YT, Zhang CF, et al. FBI-1 functions as a novel AR co-repressor in prostate cancer cells［J]. Cell Mol Life Sci, 2011, 68:1091-1103.
[54] Laudes M, Bilkovski R, Oberhauser F, et al. Transcription factor FBI-1 acts as a dual regulator in adipogenesis by coordinated regulation of cyclin-A and E2F-4［J]. J Mol Med, 2008, 86(5)： 597-608. (责任编辑狄艳红)

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