The molecular balancing act of p16(INK4a) in cancer and aging.
The molecular balancing act of p16(INK4a) in cancer and aging.
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DOI：
10.1158/1541-7786.mcr-13-0350
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Burd CE
中科院分区：
文献类型：
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作者：
LaPak KM;Burd CE
p16 INK4a位于染色体9p21.3上，似乎在一簇邻近的肿瘤抑制基因中丢失。虽然p16INK4a以抑制细胞周期蛋白依赖性激酶（CDK）活性而闻名，但它并不是一匹万能的小马。p16INK4a的长期表达促使细胞进入衰老，这是一种不可逆的细胞周期停滞，可以阻止潜在癌细胞的生长，但也有助于衰老。p16INK4a的缺失是人类肿瘤中最常见的事件之一，并允许癌前病变绕过衰老。因此，精确调节p16INK4a对组织稳态至关重要，维持肿瘤抑制和衰老之间的紧密平衡。在这里，我们概述了适当的p16INK4a调控所需的途径，并强调了p16INK4a在癌症，衰老和人类生理学中的关键功能，使该基因变得特殊。
Located on chromosome 9p21.3, p16INK4a seems lost amongst a cluster of neighboring tumor suppressor genes. While best known for inhibiting cyclin dependent kinase (CDK) activity, p16INK4a is not a one trick pony. Long term p16INK4a expression pushes cells to enter senescence, an irreversible cell cycle arrest that prevents the growth of would-be cancer cells, but also contributes to aging. Loss of p16INK4a is one of the most frequent events in human tumors and allows pre-cancerous lesions to bypass senescence. Therefore, precise regulation of p16INK4a is essential to tissue homeostasis, maintaining a tight balance between tumor suppression and aging. Here, we outline the pathways required for proper p16INK4a regulation and highlight the critical functions of p16INK4a in cancer, aging and human physiology that make this gene special.