P63
p63,亦作TP63,全称肿瘤蛋白p63(tumor protein p63)或恶性转化相关蛋白63(transformation-related protein 63),在人体内由TP63基因编码[6][7][8][9]。p63的发现是在p53基因发现后20年。p63与p53、p73同属一个蛋白家族,三者结构与功能都较为相似[10]。尽管p63的发现晚于p53,但进化生物学的证据表明p63是p53蛋白家族的起源,p53、p73都是由p63蛋白演化而成[11]。
功能
p63是p53蛋白家族下的一种转录因子。p63-/-基因型的小鼠会出现无牙、乳腺等发育依赖间充质-上皮相互作用的器官组织及无附肢等多种发育缺陷。p63蛋白的转录变体主要有两种,TAp63和ΔNp63。已证明ΔNp63拥有多种功能,包括参与皮肤发育和成体干细胞/祖细胞的功能调控[12]。相比之下,传统的观点认为TAp63的功能几乎只局限于参与凋亡过程。不过,近期的研究还表明TAp63参与了卵母细胞完整性的维持[13]。另一些研究还表明TAp63参与了心脏发育[14]和早衰过程[15]。
临床意义
p63蛋白的突变可能会导致兔唇、腭裂等发育畸形[16]。p63蛋白的突变可导致以等裂兔唇为典型特征的EEC综合征(ectrodactyly-ectodermal dysplasia-cleft syndrom)[16]。此外,p63蛋白的突变也可能导致3型兔唇腭裂综合征(EEC3)、先天性缺指(ectrodactyly,亦称为裂手-脚畸形4),以及以等裂兔唇为典型特征的AEC综合征[16]。此外,ADULT综合征(Acro–dermato–ungual–lacrimal–tooth syndrome)、附肢-乳腺综合征(limb-mammary syndrome)、RHS综合征(Rap-Hodgkin syndrome)以及也与p63蛋白功能的异常有关。目前认为兔唇、腭裂是同时出现还是任出现一种取决于p63的不同突变[16]近期,研究人员提出使用iPS细胞分化替代缺陷型上皮细胞治疗EEC综合征的方法[17]。
诊断
p63的免疫组化法可以用于诊断扁平细胞癌和前列腺腺癌(最常见的一种前列腺癌)[18]。正常的前列腺腺体含有基底细胞,因而组织高表达p63,免疫染色深,而恶性转化后的腺癌组织因缺少基底细胞,p63免疫染色呈现阴性结果[19]。p63亦可用于鉴别腺癌、小细胞癌中常见的分化程度低的癌变扁平细胞[20]。
相互作用
p63可与HNRPAB蛋白发生相互作用[21]。同样,p63可以通过与转录因子IRF6增强子结合激活其转录[16]。
调节
研究表明p63的表达受miRNAmiR-203的调控[22][23]。
参见
- AMACR,另一种前列腺癌的肿瘤标志物
参考文献
- ^ 與P63相關的疾病;在維基數據上查看/編輯參考.
- ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000073282 - Ensembl, May 2017
- ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000022510 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ Skipper M. Dedicated protection for the female germline. Nature Reviews Molecular Cell Biology. January 2007, 8 (1): 4–5. doi:10.1038/nrm2091.
- ^ Crum CP, McKeon FD. p63 in epithelial survival, germ cell surveillance, and neoplasia. Annual Review of Pathology. 2010, 5: 349–71. PMID 20078223. doi:10.1146/annurev-pathol-121808-102117.
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拓展阅读
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