TP53 P04637

细胞肿瘤抗原p53 (Antigen NY-CO-13) (磷蛋白p53) (肿瘤抑制蛋白p53)

功能描述

多功能转录因子，在结合到其靶DNA序列后诱导细胞周期停滞、DNA修复或细胞凋亡 (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:35618207, PubMed:36634798, PubMed:38653238, PubMed:9840937)。在多种肿瘤类型中作为肿瘤抑制因子；根据生理环境和细胞类型诱导生长停滞或细胞凋亡 (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17189187, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:38653238, PubMed:9840937)。通过控制该过程所需的一组基因的表达来负向调节细胞分裂 (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937)。被激活的基因之一是周期蛋白依赖性激酶的抑制剂。细胞凋亡的诱导似乎是通过刺激BAX和FAS抗原表达，或抑制Bcl-2表达来介导的 (PubMed:12524540, PubMed:17189187)。其促凋亡活性通过与PPP1R13B/ASPP1或TP53BP2/ASPP2的相互作用被激活 (PubMed:12524540)。然而，当与PPP1R13B/ASPP1或TP53BP2/ASPP2的相互作用被PPP1R13L/iASPP取代时，该活性受到抑制 (PubMed:12524540)。与线粒体PPIF合作参与激活氧化应激诱导的坏死；该功能在很大程度上不依赖于转录。诱导长链基因间非编码RNA p21 (lincRNA-p21) 和 lincRNA-Mkln1 的转录。LincRNA-p21 参与TP53依赖性的转录抑制，导致细胞凋亡，并似乎对细胞周期调节产生影响。参与Notch信号通路交叉。在DNA损伤反应中，当与CAK复合物结合时阻止CDK7激酶活性，从而停止细胞周期进程。Isoform 2 增强了 Isoform 1 在部分（而非所有）TP53诱导型启动子上的反式激活活性。Isoform 4 抑制反式激活活性，并损害由 Isoform 1 介导的生长抑制。Isoform 7 抑制 Isoform 1 介导的细胞凋亡。通过抑制CLOCK-BMAL1介导的PER2转录激活来调节生物钟 (PubMed:24051492)。 {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:17317671, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24051492, ECO:0000269|PubMed:24652652, ECO:0000269|PubMed:35618207, ECO:0000269|PubMed:36634798, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:9840937}。

组织特异性

Ubiquitous. Isoforms are expressed in a wide range of normal tissues but in a tissue-dependent manner. Isoform 2 is expressed in most normal tissues but is not detected in brain, lung, prostate, muscle, fetal brain, spinal cord and fetal liver. Isoform 3 is expressed in most normal tissues but is not detected in lung, spleen, testis, fetal brain, spinal cord and fetal liver. Isoform 7 is expressed in most normal tissues but is not detected in prostate, uterus, skeletal muscle and breast. Isoform 8 is detected only in colon, bone marrow, testis, fetal brain and intestine. Isoform 9 is expressed in most normal tissues but is not detected in brain, heart, lung, fetal liver, salivary gland, breast or intestine.

亚细胞定位

Cytoplasm