p16(INK4a)在癌症与衰老过程中的分子平衡作用
The molecular balancing act of p16(INK4a) in cancer and aging.
作者信息
LaPak Kyle M, Burd Christin E
机构信息
Biomedical Research Tower, Rm 586, The Ohio State University, 460 W. 12th Avenue, Columbus, OH 43210.
出版信息
Mol Cancer Res. 2014 Feb;12(2):167-83. doi: 10.1158/1541-7786.MCR-13-0350. Epub 2013 Oct 17.
p16(INK4a), located on chromosome 9p21.3, is lost among a cluster of neighboring tumor suppressor genes. Although it is classically known for its capacity to inhibit cyclin-dependent kinase (CDK) activity, p16(INK4a) is not just a one-trick pony. Long-term p16(INK4a) expression pushes cells to enter senescence, an irreversible cell-cycle arrest that precludes the growth of would-be cancer cells but also contributes to cellular aging. Importantly, loss of p16(INK4a) is one of the most frequent events in human tumors and allows precancerous lesions to bypass senescence. Therefore, precise regulation of p16(INK4a) is essential to tissue homeostasis, maintaining a coordinated balance between tumor suppression and aging. This review outlines the molecular pathways critical for proper p16(INK4a) regulation and emphasizes the indispensable functions of p16(INK4a) in cancer, aging, and human physiology that make this gene special.
位于9号染色体p21.3区域的p16（INK4a）在一组相邻的肿瘤抑制基因中缺失。尽管p16（INK4a）传统上以其抑制细胞周期蛋白依赖性激酶（CDK）活性的能力而闻名，但它并非只有一招。长期的p16（INK4a）表达会促使细胞进入衰老状态，这是一种不可逆的细胞周期停滞，可阻止潜在癌细胞的生长，但也会导致细胞衰老。重要的是，p16（INK4a）的缺失是人类肿瘤中最常见的事件之一，它使得癌前病变能够绕过衰老过程。因此，精确调控p16（INK4a）对于组织稳态至关重要，它能在肿瘤抑制和衰老之间维持协调平衡。本综述概述了对p16（INK4a）进行适当调控的关键分子途径，并强调了p16（INK4a）在癌症、衰老和人类生理学中的不可或缺的功能，正是这些功能使得该基因如此特殊。
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