CDKN2A是抑癌基因，编码两种独特的蛋白质，p16（Ink4a）和p14（ARF），它们在调节细胞周期进程中很重要，但是通过不同的机制调节细胞周期。p16是一种细胞周期蛋白依赖性激酶（CDK）抑制剂，通过阻止CDK4和CDK6与细胞周期蛋白的结合来抑制CDK4和CDK6；这激活视网膜母细胞瘤（Rb）蛋白质家族，其阻断G1至S期转变并可导致细胞周期停滞或静止。p14是MDM2介导的肿瘤抑制因子p53降解的抑制剂，因此增强p53依赖性反式激活和凋亡。鼠模型中CDKN2A缺失导致自发性肿瘤的产生。CDKN2A基因在许多癌症类型中也经常突变或表观遗传沉默，包括淋巴瘤，黑素瘤，胰腺癌和肺癌。此外，CDKN2A的胚系突变与家族性黑素瘤，胶质母细胞瘤和家族性胰腺癌相关。

The CDKN2A gene encodes two unique proteins, p16(Ink4a) and p14(ARF), which are important in regulating cell cycle progression. p16(Ink4a) is a cyclin-dependent kinase (CDK) inhibitor, which inhibits CDK4 and CDK6 by preventing their binding to cyclins. This activates the retinoblastoma (Rb) family of proteins, which blocks the G1 to S-phase transition and can result in cell cycle arrest or quiescence. p14(ARF) is an inhibitor of MDM2-mediated degradation of the tumor suppressor p53, thus enhancing p53-dependent transactivation and apoptosis. Deletion of CDKN2A in murine models results in the generation of spontaneous tumors, consistent with its role as a tumor suppressor. The CDKN2A locus is also frequently mutated or epigenetically silenced in numerous cancer types, including lymphoma, melanoma, pancreatic cancer, and lung cancer. Furthermore, germline mutations in CDKN2A can lead to familial pancreatic cancers.

GeneCards OncoKB My Cancer Genome