INK4a/ARF肿瘤抑制因子：一个基因——两种产物——两条通路。

The INK4a/ARF tumor suppressor: one gene--two products--two pathways.

作者信息

Chin L, Pomerantz J, DePinho R A

机构信息

Dept of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Trends Biochem Sci. 1998 Aug;23(8):291-6. doi: 10.1016/s0968-0004(98)01236-5.

DOI:10.1016/s0968-0004(98)01236-5

PMID:9757829

Abstract

Functional inactivation of the retinoblastoma (RB) and p53 pathways appears to be a rite of passage for all cancerous cells and results in disruption of cell-cycle regulation and deactivation of the apoptotic response that normally ensues. The INK4a/ARF locus sits at the nexus of these two growth-control pathways, by virtue of its ability to generate two distinct products: the p16INK4a protein, a cyclin-dependent kinase inhibitor that functions upstream of RB; and the p19ARF protein, which blocks MDM2 inhibition of p53 activity. This 'one gene--two products--two pathways' arrangement provides a basis for the prominence of INK4a/ARF in tumorigenesis.

摘要

视网膜母细胞瘤（RB）和p53信号通路的功能失活似乎是所有癌细胞必经的过程，会导致细胞周期调控紊乱以及正常情况下随之而来的凋亡反应失活。INK4a/ARF基因座处于这两条生长控制信号通路的交汇处，因为它能够产生两种不同的产物：p16INK4a蛋白，一种在RB上游起作用的细胞周期蛋白依赖性激酶抑制剂；以及p19ARF蛋白，它能阻止MDM2对p53活性的抑制。这种“一个基因——两种产物——两条信号通路”的组合为INK4a/ARF在肿瘤发生过程中的重要性提供了基础。