CDKN1A编码p21（WAF1）蛋白，其是细胞周期蛋白依赖性激酶（CDK）抑制剂Cip/Kip家族的成员。p21抑制细胞周期蛋白依赖性激酶CDC2和CDK2，导致G1期细胞周期阻滞。p21表达通过p53依赖的机制由DNA损伤而上调。此外，PI3K/Akt有丝分裂信号通路的激活导致磷酸化和p21向胞质定位，在细胞质中它不再能够进入其CDK靶点，从而导致细胞增殖增强。p21可能通过与DNA聚合酶辅助因子的相互作用在DNA损伤修复中发挥作用。p21的缺失可导致染色体非整倍体，这意味着在有丝分裂调节中起作用。p21表达在转录和蛋白水平上都受到严格调控：肿瘤抑制基因和癌基因蛋白调节CDKN1A的转录，而翻译后P21修饰调节蛋白酶体降解和亚细胞定位。在癌症中大多数p21的改变是截短的；并且p21敲除小鼠模型显示出多种癌症的发病率增加，表明P21具有抑癌作用。但在某些情况下，p21也表现出抗细胞凋亡活性，表明它还具有致癌作用。

The CDKN1A gene encodes the p21 (WAF1) protein, which is a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors. p21 inhibits the cyclin-dependent kinases CDC2 and CDK2, leading to G1 phase cell cycle arrest. p21 expression is upregulated by DNA damage through a p53-dependent mechanism. Moreover, activation of the PI3K/AKT mitogenic signaling pathway results in phosphorylation and localization of p21 to the cytoplasm where it can no longer access its CDK targets, leading to enhanced cell proliferation. p21 may play a role in repair of DNA damage through interactions with DNA polymerase accessory factors. Loss of p21 can lead to chromosomal aneuploidy, implying a role in mitotic regulation. p21 expression is tightly regulated at both the transcriptional and protein levels: tumor suppressors and oncoproteins modulate transcription of CDKN1A while post-translational p21 modification regulates proteasomal degradation and subcellular localization. The majority of p21 alterations in cancer are truncating, concurrent with its role as a tumor suppressor, and p21 knockout mouse models display an increased incidence of a variety of cancers as compared to mice with intact p21 expression. p21 also exhibits anti-apoptotic activity in certain contexts, suggesting that it also possesses an oncogenic role. Inhibitors targeting the checkpoint kinase Chk1 in combination with chemotherapy have been found to have anti-tumor activity in bladder cancer.

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