INK4a/ARF:: A multifunctional tumor suppressor locus

被引:331
作者
Sharpless, NE [1 ]
机构
[1] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
aging; p14(ARF); CDK4; MDM2;
D O I
10.1016/j.mrfmmm.2004.08.021
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The INK4a/ARF locus encodes two physically linked tumor suppressor proteins, p16(INK4a) and ARF, which regulate the RB and p53 pathways, respectively. The unusual genomic relationship of the open reading frames of these proteins initially fueled speculation that only one of the two was the true tumor suppressor, and loss of the other merely coincidental in cancer. Recent human and mouse genetic data, however, have firmly established that both proteins possess significant in vivo tumor suppressor activity, although there appear to be species- and cell-type specific differences between the two. For example, ARF plays a clear role in preventing Myc-induced lymphomagenesis in mice, whereas the role for p 16(INK4a) is human carcinomas is more firmly established. In this review, I discuss the evolutionary history of the locus, the relative importance of these tumor suppressor genes in human cancer, and recent information suggesting novel biochemical and physiologic functions of these proteins in vivo. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:22 / 38
页数:17
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