nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo journalinfonormal searchdiv searchzone qikanlogo popupnotification paper paperNew
2023, 08, v.53;No.351 1-7
调节因子X蛋白家族的结构与功能
基金项目(Foundation): 国家重点研究发展计划项目(2018YFD0900502)资助~~
邮箱(Email):
DOI: 10.16441/j.cnki.hdxb.20220001
投稿时间: 2022-01-02
投稿日期(年): 2022
修回时间: 2022-01-20
终审时间: 2022-01-26
终审日期(年): 2022
审稿周期(年): 1
移动端阅读
摘要:

调节因子X(Regulatory Factor X, RFX)蛋白家族是一类包含高度保守的有翼螺旋型DNA结合域的转录因子,因特异性结合基因启动子区的X盒而得名。该蛋白家族广泛分布于动物和真菌中,参与纤毛和精子发生、免疫反应以及细胞周期调控等多种生物过程。RFX家族的一些成员还对肿瘤细胞的存活及增殖起到促进或抑制作用,有望成为治疗肿瘤的新靶点。本文将对RFX蛋白家族的发现、各成员的结构特征、表达模式和生物学功能等进行综述,以期待为后续研究提供参考。

Abstract:

Regulatory Factor X(RFX) protein family is a class of transcription factors which contain a highly conserved DNA binding domains of the winged-helix type. RFX proteins can specifically bind the X-box motifs of the gene promoter region. RFX protein family is widely distributed in animals and fungi and is involved in various biological processes such as occurrence of cilia and spermatogenesis, immune response, and cell cycle regulation. Some members of the RFX family also promote or inhibit the survival and proliferation of tumor cells, which is expected to be the new targets for tumor treatment. In this paper, we reviewed the discovery, structural characteristics, expression patterns and biological functions of the RFX protein family in order to provide references for subsequent studies.

参考文献

[1] Rodriguez-Caso C,Medina M A,Solé R.Topology,tinkering and evolution of the human transcription factor network[J].FEBS Journal,2010,272(24):6423-6434.

[2] Tsang S Y,Nakanishi M,Peterlin B M.Mutational analysis of the DRA promoter:Cis-acting sequences and trans-acting factors[J].Molecular & Cellular Biology,1990,10(2):711-719.

[3] Reith W,Barras E,Satola S,et al.Cloning of the major histocompatibility complex classⅡ promoter binding protein affected in a hereditary defect in classⅡ gene regulation[J].Proceedings of The National Academy of Sciences of the United States of America,1989,86(11):4200-4204.

[4] Reith W,Satola S,Sanchez C H,et al.Congenital immunodeficiency with a regulatory defect in MHC classⅡ gene expression lacks a specific HLA-DR promoter binding protein,RF-X[J].Cell,1988,53(6):897-906.

[5] Ostapchuk P,Scheirle G,Hearing P.Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region[J].Molecular and Cellular Biology,1989,9(7):2787-2797.

[6] Siegrist C A,Durand B,Emery P,et al.RFX1 is identical to enhancer factor C and functions as a transactivator of the hepatitis B virus enhancer[J].Molecular and Cellular Biology,1993,13(10):6375-6384.

[7] Reith W,Ucla C,Barras E,et al.Rfx1,a transactivator of hepatitis-B virus enhancer-Ⅰ,belongs to a novel family of homodimeric and heterodimeric DNA-binding proteins[J].Molecular and Cellular Biology,1994,14(2):1230-1244.

[8] Pugliatti L,Derre J,Berger R,et al.The genes for MHC classⅡ regulatory factors RFX1 and RFX2 are located on the short arm of chromosome 19[J].Genomics,1992,13(4):1307-1310.

[9] Dotzlaw H,Alkhalaf M,Murphy L C.Characterization of estrogen receptor variant mRNAs from human breast cancers[J].Molecular Endocrinology,1992,6(5):773-785.

[10] Morotomi-Yano K,Yano K I,Saito H,et al.Human regulatory factor X4 (RFX4) is a testis-specific dimeric DNA-binding protein that cooperates with other human RFX members[J].Journal of Biological Chemistry,2002,277(1):836.

[11] Steimle V,Durand B,Barras E,et al.A novel DNA-binding regulatory factor is mutated in primary MHC classⅡ deficiency (bare lymphocyte syndrome)[J].Genes & Development,1995,9(9):1021.

[12] Chu J,Lucie S,Syed A,et al.Identification and characterization of novel human tissue-specific RFX transcription factors[J].BMC Evolutionary Biology,2008,8(1):226.

[13] Smith S B,Qu H Q,Taleb N,et al.Rfx6 directs islet formation and insulin production in mice and humans[J].Nature,2011,463(5):775-780.

[14] Soyer J,Flasse L,Raffelsberger W,et al.Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development[J].Development,2010,137(2):203-212.

[15] Smith S B,Qu H Q,Taleb N,et al.Rfx6 directs islet formation and insulin production in mice and humans[J].Nature,2010,463(7282):775-780.

[16] Castro W,Chelbi S T,Niogret C,et al.The transcription factor Rfx7 limits metabolism of NK cells and promotes their maintenance and immunity[J].Nature Immunology,2018,19(8):809.

[17] Sugiaman-Trapman D,Vitezic M,Jouhilahti E M,et al.Characterization of the human RFX transcription factor family by regulatory and target gene analysis[J].BMC Genomics,2018,19(1):181.

[18] Piasecki B P,Burghoorn J,Swoboda P.Regulatory Factor X (RFX)-mediated transcriptional rewiring of ciliary genes in animals[J].Proceedings of the National Academy of Sciences of the United States of America,2010,107(29):12969-12974.

[19] Durand B,Vandaele C,Spencer D,et al.Cloning and characterization of dRFX,the Drosophila member of the RFX family of transcription factors[J].Gene,2000,246(1-2):285-293.

[20] Reith W,Herrero-Sanchez C,Kobr M,et al.MHC classⅡ regulatory factor RFX has a novel DNA-binding domain and a functionally independent dimerization domain[J].Genes & Development,1990,4(9):1528-1540.

[21] Chen L,Smith L,Johnson M R,et al.activation of protein kinase c induces nuclear translocation of RFX1 and down-regulates c-myc via an intron 1 X box in undifferentiated leukemia hl-60 cells[J].Journal of Biological Chemistry,2018,275(41):32227-32233.

[22] Iwama A,Jing P,Pu Z,et al.Dimeric RFX proteins contribute to the activity and lineage specificity of the interleukin-5 receptor alpha promoter through activation and repression domains[J].Molecular and Cellular Biology,1999,19(6):3940-3950.

[23] Sengupta P K,Ehrlich M,Smith B D.A methylation-responsive MDBP/RFX site is in the first exon of the collagen α2(Ⅰ) promoter[J].Journal of Biological Chemistry,1999,274(51):36649.

[24] Zhang X Y,Jabrane-Ferrat N,Asiedu C K,et al.The major histocompatibility complex classⅡ promoter-binding protein RFX (NF-X) is a methylated DNA-binding protein[J].Molecular & Cellular Biology,1993,13(11):6810.

[25] Chung M I,Peyrot S M,LeBoeuf S,et al.RFX2 is broadly required for ciliogenesis during vertebrate development[J].Developmental Biology,2012,363(1):155-165.

[26] Bisgrove B W,Makova S,Yost H J,et al.RFX2 is essential in the ciliated organ of asymmetry and an RFX2 transgene identifies a population of ciliated cells sufficient for fluid flow[J].Developmental Biology,2012,363(1):166-178.

[27] Sedykh I,Keller A N,Yoon B,et al.Zebrafish Rfx4 controls dorsal and ventral midline formation in the neural tube[J].Developmental Dynamics,2018,247(4):650-659.

[28] 曹木青,潘俊敏.纤毛及纤毛相关疾病研究进展[J].中国细胞生物学学报,2012,34(9):849-856.Cao M Q,Pan J M.Cilia and ciliopathies[J].Chinese Journal of Cell Biology 2012,34(9):849-856.

[29] Swoboda P,Adler H T,Thomas J H.The RFX-type transcription factor DAF-19 regulates sensory neuron cilium formation in C.elegans[J].Molecular Cell,2000,5(3):411-421.

[30] Dubruille R,Laurenon A,Vandaele C,et al.Drosophila regulatory factor X is necessary for ciliated sensory neuron differentiation[J].Development,2003,129(23):5487-5498.

[31] Baas D,Meiniel A,Benadiba C,et al.A deficiency in RFX3 causes hydrocephalus associated with abnormal differentiation of ependymal cells[J].European Journal of Neuroscience,2010,24(4):

[32] El Zein L,Ait-Lounis A,Morle L,et al.RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies[J].Journal of Cell Science,2009,122(Pt17):3180-3189.

[33] Ait-Lounis A,Baas D,Barras E,et al.Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreas[J].Diabetes,2007,56(4):950-959.

[34] Bonnafe E,Touka M,AitLounis A,et al.The transcription factor RFX3 directs nodal cilium development and left-right asymmetry specification[J].Molecular and Cell Biology,2004,24(10):4417-4427.

[35] Essner J J,Vogan K J,Wagner M K,et al.Conserved function for embryonic nodal cilia[J].Nature,2002,418(6893):37-38.

[36] Yu X W,Ng C P,Habacher H,et al.Foxj1 transcription factors are master regulators of the motile ciliogenic program[J].Nature Genetics,2008,40(12):1445-1453.

[37] Hellman N E,Liu Y,Merkel E,et al.The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch[J].Proceedings of the National Academy of Sciences,2010,107(43):18499-18504.

[38] Ashique A M,Choe Y,Karlen M,et al.The Rfx4 transcription factor modulates shh signaling by regional control of ciliogenesis[J].Science Signaling,2009,2(95):70.

[39] Manojlovic Z,Earwood R,Kato A,et al.RFX7 is required for the formation of cilia in the neural tube[J].Mechanisms of Development,2014,132:28-37.

[40] Purvis T L,Hearn T,Spalluto C,et al.Transcriptional regulation of the alstr?m syndrome gene ALMS1 by members of the RFX family and Sp1[J].Gene,2010,460(1-2):20-29.

[41] Neto F T L,Bach P V,Najari B B,et al.Spermatogenesis in humans and its affecting factors[J].Seminars in Cell & Developmental Biology,2016,59:10-26.

[42] Kistler W S,Horvath G C,Dasgupta A,et al.Differential expression of Rfx1—4 during mouse spermatogenesis[J].Gene Expression Patterns,2009,9(7):515-519.

[43] Bellora N,Farré D,Albà M.Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters[J].BMC Genomics,2007,8(1):459.

[44] Horvath G C,Kistler W S,Kistler M K.RFX2 is a potential transcriptional regulatory factor for histone H1t and other genes expressed during the meiotic phase of spermatogenesis[J].Biology Reprodction,2004,71(5):1551-1559.

[45] Wolfe S A,van Wert J,Grimes S R.Transcription factor RFX2 is abundant in rat testis and enriched in nuclei of primary spermatocytes where it appears to be required for transcription of the testis-specific histone H1t gene[J].Journal of Cellular Biochemistry,2006,99(3):735-746.

[46] Grimes S,Weisz-Carrington P,Daum H,et al.A rat histone H4 gene closely associated with the testis-specific H1t gene[J].Experimental Cell Research,1987,173(2):534-545.

[47] Horvath G C,Kistler M K,Kistler W S.RFX2 is a candidate downstream amplifier of A-MYB regulation in mouse spermatogenesis[J].BMC Developmental Biology,2009,9(1):63.

[48] Wu Y,Hu X,Li Z,et al.Transcription factor RFX2 is a key regulator of mouse spermiogenesis[J].Scientific Reports,2015,6:20435.

[49] Kistler W S,Baas D,Lemeille S,et al.RFX2 Is a Major Transcriptional Regulator of Spermiogenesis[J].PLoS Genetics,2015,11(7):e1005368.

[50] Jiang J,Zhang N,Shiba H,et al.Spermatogenesis associated 4 promotes sertoli cell proliferation modulated negatively by regulatory factor X1[J].PLoS One,2013,8(10):e75933.

[51] Wang B,Qi T,Chen S Q,et al.RFX1 maintains testis cord integrity by regulating the expression of Itga6 in male mouse embryos[J].Molecular Reproduction & Development,2016,83(7):606-6142.

[52] Wolfe S A,Vanwert J M,Grimes S R.Transcription factor RFX4 binding to the testis-specific histone H1t promoter in spermatocytes may be important for regulation of H1t gene transcription during spermatogenesis[J].Journal of Cellular Biochemistry,2010,105(1):61-69.

[53] Xie Y,Moussaif M,Choi S,et al.RFX transcription factor DAF-19 regulates 5-HT and innate immune responses to pathogenic bacteria in Caenorhabditis elegans[J].PLoS Genet,2013,9(3):e1003324.

[54] Villard J,Mach B,Reith W.MHC classⅡ deficiency:Definition of a new complementation group[J].Immunobiology,1997,198(1-3):264-272.

[55] Knight,Julian,C,et al.Genomic mapping of the MHC transactivator CIITA using an integrated ChIP-seq and genetical genomics[J].Genome Biology,2014,15:494.

[56] Nekrep N,Fontes J D,Geyer M,et al.When the lymphocyte loses its clothes[J].Immunity,2003,18(4):453-457.

[57] Devaiah B N,Singer D S.CIITA and its dual roles in MHC gene transcription[J].Frontiers in Immunology,2013,4(476):476.

[58] Beaulieu Y B,Machado J,Ethier S,et al.Degradation,promoter recruitment and transactivation mediated by the extreme N-terminus of MHC classⅡ transactivator CIITA isoformⅢ[J].PLoS One,2016,11(2):e0148753.

[59] Gao J,Xu C.Structural basis for the recognition of RFX7 by ANKRA2 and RFXANK[J].Biochemical & Biophysical Research Communications,2020,523(1):263-266.

[60] Zhao M,Tan Y,Peng Q,et al.IL-6/STAT3 pathway induced deficiency of RFX1 contributes to Th17-dependent autoimmune diseases via epigenetic regulation[J].Nature Communications,2018,9(1):583.

[61] Bugeja H E,Hynes M J,Andrianopoulos A.The RFX protein RfxA is an essential regulator of growth and morphogenesis in Penicillium marneffei[J].Eukaryotic Cell,2010,9(4):578-591.

[62] Schmitt,E.K.The fungal CPCR1 protein,which binds specifically to beta-lactam biosynthesis genes,is related to human regulatory factor X transcription factors[J].Journal of Biological Chemistry,2000,275(13):9348-9357.

[63] Wu S Y,Mcleod M.The sak1+ gene of Schizosaccharomyces pombe encodes an RFX family DNA-binding protein that positively regulates cyclic AMP-dependent protein kinase-mediated exit from the mitotic cell cycle[J].Molecular & Cellular Biology,1995,15(3):1479-1488.

[64] Huang M,Zheng Z,Elledge S J.The DNA replication and damage checkpoint p athways induce transcription by inhibition of the Crt1 repressor[J].Cell,1998,94(5):595-605.

[65] Labrie C,Lee B H,Mathews M B.Transcription factors RFX1/EF-C and ATF-1 associate with the adenovirus E1A-responsive element of the human proliferating cell nuclear antigen promoter[J].Nucleic Acids Research,1995,23(18):3732-3741.

[66] Suski J M,Braun M,Strmiska V,et al.Targeting cell-cycle machinery in cancer[J].Cancer Cell,2021,39(6):759-778.

[67] 赵杨静,谢兴旺,王荟等.调节因子X5及其复合物的研究进展[J].临床检验杂志,2017,35(5):356-359.Zhao Y J,Xie X W,Wang H,et al.[J].Chinese Journal of Clinical Laboratory Science,2017,35(5):356-359.

[68] Zhao Y J,Xie X W,Liao W J,et al.The transcription factor RFX5 is a transcriptional activator of the TPP1 gene in hepatocellular carcinoma[J].Oncology Reports,2017,37(1):289-296.

[69] Epstein F H,Blobe G C,Schiemann W P,et al.Role of transforming growth factor beta in human disease[J].New England Journal of Medicine,2000,342(18):1350-1358.

[70] Feng C,Zuo Z.Regulatory factor X1-induced down-regulation of transforming growth factor β2 transcription in human neuroblastoma cells[J].Journal of Biological Chemistry,2012,287(27):22730-22739.

[71] Su J C,Chiang H C,Tseng P H,et al.RFX-1-dependent activation of SHP-1 inhibits STAT3 signaling in hepatocellular carcinoma cells[J].Carcinogenesis,2014,35(12):2807-2814.

[72] Jeong H Y,Kim H J,Cheol-Eun K,et al.High expression of RFX4 is associated with tumor progression and poor prognosis in patients with glioblastoma[J].International Journal of Neuroscience,2020,131(10):1-11.

[73] Coronel L,Riege K,Schwab K,et al.Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress[J].Nucleic Acids Research,2021,49(13):7437-7456.

[74] Baas D,Meiniel A,Benadiba C,et al.A deficiency in RFX3 causes hydrocephalus associated with abnormal differentiation of ependymal cells[J].European Journal of Neuroscience,2006,24(4):1020-1030.

[75] Lemeille S,Paschaki M,Baas D,et al.Interplay of RFX transcription factors 1,2 and 3 in motile ciliogenesis[J].Nucleic Acids Research,2020,48(16):9019-9036.

[76] 蔡昆争,骆世明,段舜山.生命系统的功能冗余[C]//第12届全国农业生态学研讨会.广州:中国生态学会,广东省生态学会,2005:381-384.Cai K Z,Luo S M,Duan S S.Functional redundancy of living systems[C]//The 12th National Conference on Agricultural Ecology.Guangzhou:Chinese Ecological Society,Guangdong Ecological Society,2005:381-384.

[77] Lu J,Cheng C,Cheng Z C,et al.The dual role of RFX6 in directing beta cell development and insulin production[J].Journal of Molecular Endocrinology,2021,66(2):129-139.

[78] Elkon R,Milon B,Morrison L,et al.RFX transcription factors are essential for hearing in mice[J].Nature Communication,2015,6:8549.

基本信息:

DOI:10.16441/j.cnki.hdxb.20220001

中图分类号:Q75

引用信息:

[1]李红岩,尹秀,张祥敏.调节因子X蛋白家族的结构与功能[J],2023,53(08):1-7.DOI:10.16441/j.cnki.hdxb.20220001.

基金信息:

国家重点研究发展计划项目(2018YFD0900502)资助~~

投稿时间:

2022-01-02

投稿日期(年):

2022

修回时间:

2022-01-20

终审时间:

2022-01-26

终审日期(年):

2022

审稿周期(年):

1

检 索 高级检索

引用

GB/T 7714-2015 格式引文
MLA格式引文
APA格式引文