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小鼠p16^(INK4a)基因位点的结构和功能研究 被引量:4

Structure and Function of Mouse p16^(INK4a) Locus
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摘要 p1 6INK4a基因的失活与多种肿瘤的发生和发展有联系。通过筛选小鼠基因组文库 ,获得长度为 1 4.5kb的p1 6INK4a基因组DNA片段。对上述 1 4.5kbDNA测序后进行生物信息学分析表明 :该片段包含 3个外显子 ,编码 1个由 1 68个氨基酸残基组成的多肽 ,其相对分子质量的理论计算值为 1 7941 ,有 7个可能的磷酸化位点 ,说明p1 6INK4a蛋白的功能可能受到磷酸化的调控。该DNA片段的非编码区分布着大量短散布元件、长散布元件和简单重复序列 ,这样的结构为转座和同源重组提供了结构基础 ,提示了部分肿瘤细胞中p1 6INK4a基因缺失的可能原因。 Inactivation of p16 INK4a is highly related with tumors. We obtained a 14.5kb mouse genomic DNA fragment through screening the 129/SvJ mouse genomic library. Bioinformatics study suggests that the fragment contain three exons, which encode a 17?941 dolton polypeptide consisted of 168aa. The polypeptide has 7 potential phosphorylation sites, which indicates that the function of p16 INK4a itself may be under the control of phosphorylation. Many interspersed elements and simple repeats were found in the noncoding region. These elements and repeats may cause retropositon and recombination and thus be responsible for some of the p16 INK4a locus deletion. We also compared our sequence of exon 1 α with those published elsewhere and found that polymorphism may exist.
出处 《Acta Genetica Sinica》 SCIE CAS CSCD 北大核心 2001年第10期921-925,共5页
基金 上海 -联合利华研究与发展基金资助~~
关键词 P16^INK4A 磷酸化调控 基因缺失 DNA 多肽多态性 小鼠 基因结构 肿瘤性 p16 INK4a phosphorylation deletion polymorphism
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参考文献2

  • 1Zhang S,Proc Nat Acad Sci USA,1998年,95卷,2429页
  • 2Herzog C R,Mamm Genome,1997年,8卷,65页

同被引文献16

  • 1李兰,潘庆玉,沈伟,潘庆杰,周艳荣,邓继先.外源基因转染导致山羊体细胞过快衰老与端粒缩短的研究[J].中国生物工程杂志,2006,26(6):45-49. 被引量:2
  • 2Zou X G, Wang Y G, Cheng Y, Yang Y, Ju H, Tang H, Shen Y, MuZ, Xu S, Du M. Generation of cloned gouts (Gapra hircus) from transfected fetal fibroblast cell, the effect of donor cell cycle.Mol Reprod Dev, 2002, 61: 164-172.
  • 3Denning C, Bud S, Ainsline A, Bracken J, Dinnyes A, Fletcher J,King T, Ritchie M, Ritchie W A, Rollo M, de Sousa P, Travers A,Wilmut I, Clark A J. Deletion of the a (1,3) galactosyl transferase (GGTAI) gene and the priori protein (PrP) gene in sheep.Nat Biotechnol, 2001, 19: 559-562.
  • 4Fradiani P A, Ascenzioni F, Lavitrano M, Donini P. Telomeres and telomerase activity in pig tissues. Biochimie, 2004,86:7-12.
  • 5Duan J M, Zhang Z Y, Tong T J. Senescence delay of human diploid fibroblast induced by anti-sense p16^INK4a expression. J Biol Chem, 2001, 276(51): 48325- 48331.
  • 6Wang W, Wu J F, Zhang Z Y, Tong T J. Characterization of regulatory elements on the promoter region of p16^INK4a that contribute to overexpression of p16 in senescent fibroblasts. J Biol Chem,2001, 276(52): 48655-48661.
  • 7Egawa K, Kurihara Y, Ito T, Matsumoto M, Nose K. Induction of p16^INK4a transcription and of cellular senescence by aclacinomycin-derivatives and cardiac glycosides. Biol Pharm Bull, 2002,25: 461-465.
  • 8Taylor L M, James A, Schuller C E, Brce J, Lock R B,MacKenzie K L. Inactivation of p^16^INK4a, with retention of pRB and p53/p21^cipl function, in human MRC5 fibroblasts that overcome a telomere-independent crisis during immortalization. J Biol Chem, 2004, 279: 43634-43645.
  • 9Weebadda W K C, Jackson T J, Lin A W. Expression of p16^INK4A variants in senescent human fibroblasts independent of protein phosphorylation. J Cell Biochem, 2005, 94:1135-1147.
  • 10Alcorta D A, Xiong Y, Phelps D, Hannon G, Beach D, Barrett J C. Involvement of the cyclin-dependent kinase inhibitor p16^INK4a in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci USA, 1996, 93: 13742-13747.

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