TP53是一种非常重要的抑癌基因(tumor suppressor gene),属于p53基因家族,该家族还包括p63和p73等成员,它们共同的特点是编码的蛋白质都含有DNA结合结构域,能够调控细胞周期、DNA修复和细胞凋亡等关键生物学过程。TP53基因编码的p53蛋白被称为“基因组守护者”,因为它能监测细胞内的DNA损伤或其他应激信号(如缺氧或癌基因激活),并通过激活下游靶基因来阻止异常细胞的增殖。当DNA损伤发生时,p53蛋白会积累并发挥作用,主要作用位点在细胞核内,它可以暂停细胞周期(通过激活p21等基因)以允许DNA修复,若损伤无法修复则启动细胞凋亡(通过激活BAX、PUMA等基因),从而防止突变积累和肿瘤发生。TP53基因突变是癌症中最常见的遗传变异之一,约50%的人类肿瘤存在TP53突变,突变会导致p53蛋白功能丧失或获得异常功能(如促进肿瘤生长),从而增加癌症风险,如Li-Fraumeni综合征(一种遗传性癌症易感综合征)就与TP53胚系突变相关。TP53过表达通常发生在DNA损伤或应激条件下,是正常的保护性反应,但某些突变型p53的过表达可能促进肿瘤侵袭和转移;而TP53表达降低或缺失会导致基因组不稳定、细胞凋亡受阻,加速肿瘤发展。此外,TP53还参与调控代谢、衰老和免疫应答等过程,其功能异常可能影响这些生理活动。p53基因家族的成员在结构上相似,但功能各有侧重,例如p63和p73更多参与发育和分化调控。
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TP53基因(以及对应的蛋白质)的细胞分布位置:
TP53基因的本体(GO)信息:
| 名称 |
|---|
| 4010 MAPK signaling pathway [PATH:hsa04010] |
| 4310 Wnt signaling pathway [PATH:hsa04310] |
| 4071 Sphingolipid signaling pathway [PATH:hsa04071] |
| 4151 PI3K-Akt signaling pathway [PATH:hsa04151] |
| 4110 Cell cycle [PATH:hsa04110] |
| 4210 Apoptosis [PATH:hsa04210] |
| 4115 p53 signaling pathway [PATH:hsa04115] |
| 4919 Thyroid hormone signaling pathway [PATH:hsa04919] |
| 4722 Neurotrophin signaling pathway [PATH:hsa04722] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5230 Central carbon metabolism in cancer [PATH:hsa05230] |
| 5202 Transcriptional misregulation in cancers [PATH:hsa05202] |
| 5206 MicroRNAs in cancer [PATH:hsa05206] |
| 5205 Proteoglycans in cancer [PATH:hsa05205] |
| 5203 Viral carcinogenesis [PATH:hsa05203] |
| 5210 Colorectal cancer [PATH:hsa05210] |
| 5212 Pancreatic cancer [PATH:hsa05212] |
| 5214 Glioma [PATH:hsa05214] |
| 5216 Thyroid cancer [PATH:hsa05216] |
| 5220 Chronic myeloid leukemia [PATH:hsa05220] |
| 5217 Basal cell carcinoma [PATH:hsa05217] |
| 5218 Melanoma [PATH:hsa05218] |
| 5219 Bladder cancer [PATH:hsa05219] |
| 5215 Prostate cancer [PATH:hsa05215] |
| 5213 Endometrial cancer [PATH:hsa05213] |
| 5222 Small cell lung cancer [PATH:hsa05222] |
| 5223 Non-small cell lung cancer [PATH:hsa05223] |
| 5014 Amyotrophic lateral sclerosis (ALS) [PATH:hsa05014] |
| 5016 Huntington's disease [PATH:hsa05016] |
| 5166 HTLV-I infection [PATH:hsa05166] |
| 5162 Measles [PATH:hsa05162] |
| 5161 Hepatitis B [PATH:hsa05161] |
| 5160 Hepatitis C [PATH:hsa05160] |
| 5168 Herpes simplex infection [PATH:hsa05168] |
| 5169 Epstein-Barr virus infection [PATH:hsa05169] |
| 名称 |
|---|
| Activation of BH3-only proteins |
| Activation of NOXA and translocation to mitochondria |
| Activation of PUMA and translocation to mitochondria |
| Apoptosis |
| Autodegradation of the E3 ubiquitin ligase COP1 |
| Cell Cycle |
| Cell Cycle Checkpoints |
| Cellular responses to stress |
| Cellular Senescence |
| DNA Damage/Telomere Stress Induced Senescence |
| Factors involved in megakaryocyte development and platelet production |
| Formation of Senescence-Associated Heterochromatin Foci (SAHF) |
| G1/S DNA Damage Checkpoints |
| Gene Expression |
| Generic Transcription Pathway |
| Hemostasis |
| Intrinsic Pathway for Apoptosis |
| Oncogene Induced Senescence |
| Oxidative Stress Induced Senescence |
| p53-Dependent G1 DNA Damage Response |
| p53-Dependent G1/S DNA damage checkpoint |
| Pre-NOTCH Expression and Processing |
| Pre-NOTCH Transcription and Translation |
| Programmed Cell Death |
| Signaling by NOTCH |
| Stabilization of p53 |
| TP53 Regulates Metabolic Genes |
| Transcriptional activation of cell cycle inhibitor p21 |
| Transcriptional activation of p53 responsive genes |
| Transcriptional Regulation by TP53 |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Liver carcinoma | 0.511429968 | 527 | 4 | BeFree_CLINVAR_CTD_human_CTD_mouse_GAD_LHGDN |
| Adenocarcinoma | 0.510581136 | 347 | 2 | BeFree_CLINVAR_CTD_human_CTD_mouse_GAD_LHGDN |
| LI-FRAUMENI SYNDROME 1 | 0.440542884 | 21 | 33 | BeFree_CLINVAR_CTD_human_MGD_UNIPROT |
| Squamous cell carcinoma | 0.44 | 632 | 3 | BeFree_CTD_human_CTD_mouse_GAD_LHGDN |
| Sarcoma | 0.400032709 | 173 | 3 | BeFree_CLINVAR_CTD_human_CTD_mouse_GAD_LHGDN |
| Osteosarcoma | 0.382163696 | 143 | 13 | BeFree_CLINVAR_CTD_human_GAD_LHGDN_MGD |
| Li-Fraumeni Syndrome | 0.36854679 | 308 | 26 | BeFree_CLINVAR_GAD_LHGDN_ORPHANET |
| Choroid Plexus Papilloma | 0.365634266 | 3 | 0 | BeFree_CLINVAR_CTD_human_GAD_LHGDN_ORPHANET |
| Stomach Neoplasms | 0.364021203 | 55 | 1 | BeFree_CLINVAR_CTD_human_GAD_LHGDN |
| Mammary Neoplasms | 0.352996796 | 247 | 6 | BeFree_CTD_human_CTD_mouse_GAD_LHGDN |
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