P63

p63，亦作TP63，全稱腫瘤蛋白p63（tumor protein p63）或惡性轉化相關蛋白63（transformation-related protein 63），在人體內由TP63基因編碼。p63的發現是在p53基因發現後20年。p63與p53、p73同屬一個蛋白家族，三者結構與功能都較爲相似。儘管p63的發現晚於p53，但進化生物學的證據表明p63是p53蛋白家族的起源，p53、p73都是由p63蛋白演化而成。 p63是p53蛋白家族下的一種轉錄因子。p63-/-基因型的小鼠會出現無牙、乳腺等發育依賴間充質-上皮相互作用的器官組織及無附肢等多種發育缺陷。p63蛋白的轉錄變體主要有兩種，TAp63和ΔNp63。已證明ΔNp63擁有多種功能，包括參與皮膚發育和成體幹細胞/祖細胞的功能調控。相比之下，傳統的觀點認爲TAp63的功能幾乎只侷限於參與凋亡過程。不過，近期的研究還表明TAp63參與了卵母細胞完整性的維持。另一些研究還表明TAp63參與了心臟發育和早衰過程。 p63蛋白的突變可能會導致兔脣、腭裂等發育畸形。p63蛋白的突變可導致以等裂兔脣爲典型特徵的EEC綜合徵（英语：ectrodactyly-ectodermal dysplasia-cleft syndrome）（ectrodactyly-ectodermal dysplasia-cleft syndrom）。此外，p63蛋白的突變也可能導致3型兔脣腭裂綜合徵（英语：cleft lip/palate syndrome 3）（EEC3）、先天性缺指（英语：ectrodactyly）（ectrodactyly，亦稱爲裂手-腳畸形4），以及以等裂兔脣爲典型特徵的AEC綜合徵（英语：Hay–Wells syndrome）。此外，ADULT綜合徵（英语：Acro–dermato–ungual–lacrimal–tooth syndrome）（Acro–dermato–ungual–lacrimal–tooth syndrome）、附肢-乳腺綜合徵（英语：limb-mammary syndrome）（limb-mammary syndrome）、RHS綜合徵（英语：Rap-Hodgkin syndrome）（Rap-Hodgkin syndrome）以及也與p63蛋白功能的異常有關。目前認爲兔脣、腭裂是同時出現還是任出現一種取決於p63的不同突變近期，研究人員提出使用iPS細胞分化替代缺陷型上皮細胞治療EEC綜合徵的方法。 p63的免疫組化法可以用於診斷扁平細胞癌和前列腺腺癌（最常見的一種前列腺癌）。正常的前列腺腺體含有基底細胞，因而組織高表達p63，免疫染色深，而惡性轉化後的腺癌組織因缺少基底細胞，p63免疫染色呈現陰性結果。p63亦可用於鑑別腺癌、小細胞癌中常見的分化程度低的癌變扁平細胞。 p63可與HNRPAB（英语：HNRPAB）蛋白發生相互作用。同樣，p63可以通過與轉錄因子IRF6（英语：IRF6）增強子結合激活其轉錄。 研究表明p63的表達受miRNAmiR-203（英语：miR-203）的調控。 AMACR（英语：AMACR），另一種前列腺癌的腫瘤標誌物 與P63相關的疾病；在維基數據上查看/編輯參考.  GRCh38: Ensembl release 89: ENSG00000073282 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000022510 - Ensembl, May 2017 Human PubMed Reference:. 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PMID 21127502. doi:10.1038/cdd.2010.159.  醫學主題詞表（MeSH）：TP73L+protein,+human GeneReviews/NCBI/NIH/UW entry on Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Syndrome or AEC Syndrome, Hay-Wells Syndrome. Includes: Rapp-Hodgkin Syndrome（页面存档备份，存于互联网档案馆） OMIM entries on AEC