P63

P63
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	4A9Z、1RG6、2RMN、2Y9T、2Y9U、3QYM、3QYN、3US0、3US1、3US2、3ZY0、3ZY1
識別號
别名	TP63；, AIS, B(p51A), B(p51B), EEC3, KET, LMS, NBP, OFC8, RHS, SHFM4, TP53CP, TP53L, TP73L, p40, p51, p53CP, p63, p73H, p73L, tumor protein p63
外部ID	OMIM：603273 MGI：1330810 HomoloGene：31189 GeneCards：TP63
相關疾病
	肺腺癌、lymphoblastic leukemia、肺癌、ADULT綜合徵、附肢-乳腺綜合徵、AEC綜合徵、split hand-foot malformation 2[1]
基因位置（人类）
染色体	3號染色體[2]
终止	189,897,276 bp[2]
基因位置（小鼠）
染色体	小鼠16号染色体[3]
终止	25,710,852 bp[3]
RNA表达模式
	; ; ; ;
	查阅更多表达数据
基因本體
分子功能	• DNA-binding transcription activator activity, RNA polymerase II-specific; • 金屬離子結合; • damaged DNA binding; • 血浆蛋白结合; • WW domain binding; • double-stranded DNA binding; • DNA结合; • sequence-specific DNA binding; • 相同蛋白质结合; • chromatin binding; • p53 binding; • DNA结合转录因子活性; • MDM2/MDM4 family protein binding; • DNA-binding transcription factor activity, RNA polymerase II-specific; • protein domain specific binding;
細胞組分	• 細胞質; • neuron projection; • 细胞核; • 粗面内质网; • 轉錄調節複合物; • 核质; • 树突; • 線粒體; • 高尔基体; • 细胞质基质; • 大分子复合体;
生物學過程	• pattern specification process; • 骨骼系统的发生; • epithelial cell development; • negative regulation of keratinocyte differentiation; • epidermal cell division; • anatomical structure formation involved in morphogenesis; • prostate gland development; • transcription by RNA polymerase II; • squamous basal epithelial stem cell differentiation involved in prostate gland acinus development; • ectoderm and mesoderm interaction; • cellular response to DNA damage stimulus; • female genitalia morphogenesis; • odontogenesis of dentin-containing tooth; • prostatic bud formation; • positive regulation of cell cycle G1/S phase transition; • positive regulation of mesenchymal cell proliferation; • 精子发生; • multicellular organism aging; • smooth muscle tissue development; • positive regulation of fibroblast apoptotic process; • animal organ morphogenesis; • hair follicle morphogenesis; • positive regulation of Notch signaling pathway; • 细胞凋亡; • 染色体重建; • regulation of transcription, DNA-templated; • regulation of neuron apoptotic process; • positive regulation of apoptotic signaling pathway; • regulation of cysteine-type endopeptidase activity involved in apoptotic process; • transcription, DNA-templated; • embryonic limb morphogenesis; • negative regulation of mesoderm development; • epidermis development; • post-anal tail morphogenesis; • response to gamma radiation; • protein homotetramerization; • Notch信号通路; • hair follicle development; • neuron apoptotic process; • polarized epithelial cell differentiation; • proximal/distal pattern formation; • 细胞分化; • positive regulation of keratinocyte proliferation; • skin morphogenesis; • epithelial cell differentiation; • 膀胱的发生; • cellular response to UV; • establishment of planar polarity; • negative regulation of apoptotic process; • negative regulation of transcription by RNA polymerase II; • protein tetramerization; • keratinocyte proliferation; • positive regulation of osteoblast differentiation; • regulation of epidermal cell division; • negative regulation of transcription, DNA-templated; • negative regulation of cellular senescence; • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; • sympathetic nervous system development; • establishment of skin barrier; • morphogenesis of a polarized epithelium; • keratinocyte differentiation; • multicellular organism development; • mitotic G1 DNA damage checkpoint signaling; • cloacal septation; • response to X-ray; • positive regulation of transcription by RNA polymerase II; • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; • regulation of signal transduction by p53 class mediator; • regulation of apoptotic process; • 老化; • negative regulation of intracellular estrogen receptor signaling pathway; • positive regulation of transcription, DNA-templated; • positive regulation of somatic stem cell population maintenance; • 細胞增殖; • epidermal cell differentiation; • embryonic forelimb morphogenesis; • embryonic hindlimb morphogenesis; • skin epidermis development; • cranial skeletal system development; • 发育过程;
	Sources:Amigo / QuickGO
直系同源
	8626
	22061
	ENSG00000073282
	ENSMUSG00000022510
	Q9H3D4
	O88898
NM_001114978; NM_001114979; NM_001114980; NM_001114981; NM_001114982;
	NM_003722; NM_001329144; NM_001329145; NM_001329146; NM_001329148; NM_001329149; NM_001329150; NM_001329964
NM_001127259; NM_001127260; NM_001127261; NM_001127262; NM_001127263;
	NM_001127264; NM_001127265; NM_011641
NP_001108450; NP_001108451; NP_001108452; NP_001108453; NP_001108454;
	NP_001316073; NP_001316074; NP_001316075; NP_001316077; NP_001316078; NP_001316079; NP_001316893; NP_003713
NP_001120731; NP_001120732; NP_001120733; NP_001120734; NP_001120735;
	NP_001120736; NP_001120737; NP_035771
	維基數據

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[6][7][8][9]。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[10]。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[11]。

功能

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[12]。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[13]。另一些研究還表明TAp63參與了心臟發育[14]和早衰過程[15]。

臨床意義

p63蛋白的突變可能會導致兔脣、腭裂等發育畸形[16]。p63蛋白的突變可導致以等裂兔脣爲典型特徵的EEC綜合徵（ectrodactyly-ectodermal dysplasia-cleft syndrom）[16]。此外，p63蛋白的突變也可能導致3型兔脣腭裂綜合徵（EEC3）、先天性缺指（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[16]。此外，ADULT綜合徵（Acro–dermato–ungual–lacrimal–tooth syndrome）、附肢-乳腺綜合徵（limb-mammary syndrome）、RHS綜合徵（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[16]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[17]。

診斷

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）[18]。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[19]。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[20]。

相互作用

p63可與HNRPAB蛋白發生相互作用[21]。同樣，p63可以通過與轉錄因子IRF6增強子結合激活其轉錄[16]。

調節

研究表明p63的表達受miRNAmiR-203的調控[22][23]。

參見

AMACR，另一種前列腺癌的腫瘤標誌物

参考文献

.
GRCh38: Ensembl release 89: ENSG00000073282 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000022510 - Ensembl, May 2017
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. National Center for Biotechnology Information, U.S. National Library of Medicine.
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Zeng X, Zhu Y, Lu H. . Carcinogenesis. Feb 2001, 22 (2): 215–9. PMID 11181441. doi:10.1093/carcin/22.2.215.
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Wu G, Nomoto S, Hoque MO, Dracheva T, Osada M, Lee CC, Dong SM, Guo Z, Benoit N, Cohen Y, Rechthand P, Califano J, Moon CS, Ratovitski E, Jen J, Sidransky D, Trink B. . Cancer Research. May 2003, 63 (10): 2351–7. PMID 12750249.
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Su X, Paris M, Gi YJ, Tsai KY, Cho MS, Lin YL, Biernaskie JA, Sinha S, Prives C, Pevny LH, Miller FD, Flores ER. . Cell Stem Cell. Jul 2009, 5 (1): 64–75. PMC 3418222 . PMID 19570515. doi:10.1016/j.stem.2009.04.003.
Dixon MJ, Marazita ML, Beaty TH, Murray JC. . Nature Reviews Genetics. Mar 2011, 12 (3): 167–78. PMC 3086810 . PMID 21331089. doi:10.1038/nrg2933.
Shalom Feuerstein R. et al. Impaired epithelial differentiation of induced pluripotent stem cells from EEC patients is rescued by APR-246/PRIMA-1MET. P.N.A.S 2012. . [2014-12-13]. （原始内容存档于2014-12-14）.
Shiran MS, Tan GC, Sabariah AR, Rampal L, Phang KS. . The Medical Journal of Malaysia. Mar 2007, 62 (1): 36–9. PMID 17682568.
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Yi R, Poy MN, Stoffel M, Fuchs E. . Nature. Mar 2008, 452 (7184): 225–9. PMID 18311128. doi:10.1038/nature06642.
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拓展閱讀

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外部链接

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[1] .

[refGRCh38Ensembl-2] GRCh38: Ensembl release 89: ENSG00000073282 - Ensembl, May 2017

[refGRCm38Ensembl-3] GRCm38: Ensembl release 89: ENSMUSG00000022510 - Ensembl, May 2017

[4] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9774969-6] Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dötsch V, Andrews NC, Caput D, McKeon F. . Molecular Cell. Sep 1998, 2 (3): 305–16. PMID 9774969. doi:10.1016/S1097-2765(00)80275-0.

[pmid9662378-7] Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M, Ikawa S. . Nature Medicine. Jul 1998, 4 (7): 839–43. PMID 9662378. doi:10.1038/nm0798-839.

[pmid11181441-8] Zeng X, Zhu Y, Lu H. . Carcinogenesis. Feb 2001, 22 (2): 215–9. PMID 11181441. doi:10.1093/carcin/22.2.215.

[pmid11181451-9] Tan M, Bian J, Guan K, Sun Y. . Carcinogenesis. Feb 2001, 22 (2): 295–300. PMID 11181451. doi:10.1093/carcin/22.2.295.

[pmid12750249-10] Wu G, Nomoto S, Hoque MO, Dracheva T, Osada M, Lee CC, Dong SM, Guo Z, Benoit N, Cohen Y, Rechthand P, Califano J, Moon CS, Ratovitski E, Jen J, Sidransky D, Trink B. . Cancer Research. May 2003, 63 (10): 2351–7. PMID 12750249.

[Skipper_2007-11] Skipper M. . Nature Reviews Molecular Cell Biology. January 2007, 8 (1): 4–5. doi:10.1038/nrm2091.

[pmid20078223-12] Crum CP, McKeon FD. . Annual Review of Pathology. 2010, 5: 349–71. PMID 20078223. doi:10.1146/annurev-pathol-121808-102117.

[pmid21335238-13] Deutsch GB, Zielonka EM, Coutandin D, Weber TA, Schäfer B, Hannewald J, Luh LM, Durst FG, Ibrahim M, Hoffmann J, Niesen FH, Sentürk A, Kunkel H, Brutschy B, Schleiff E, Knapp S, Acker-Palmer A, Grez M, McKeon F, Dötsch V. . Cell. Feb 2011, 144 (4): 566–76. PMC 3087504 . PMID 21335238. doi:10.1016/j.cell.2011.01.013.

[pmid21898690-14] Rouleau M, Medawar A, Hamon L, Shivtiel S, Wolchinsky Z, Zhou H, De Rosa L, Candi E, de la Forest Divonne S, Mikkola ML, van Bokhoven H, Missero C, Melino G, Pucéat M, Aberdam D. . Stem Cells. Nov 2011, 29 (11): 1672–83 [2017-11-13]. PMID 21898690. doi:10.1002/stem.723. （原始内容存档于2014-08-08）.

[pmid19570515-15] Su X, Paris M, Gi YJ, Tsai KY, Cho MS, Lin YL, Biernaskie JA, Sinha S, Prives C, Pevny LH, Miller FD, Flores ER. . Cell Stem Cell. Jul 2009, 5 (1): 64–75. PMC 3418222 . PMID 19570515. doi:10.1016/j.stem.2009.04.003.

[Dixon_2011-16] Dixon MJ, Marazita ML, Beaty TH, Murray JC. . Nature Reviews Genetics. Mar 2011, 12 (3): 167–78. PMC 3086810 . PMID 21331089. doi:10.1038/nrg2933.

[17] Shalom Feuerstein R. et al. Impaired epithelial differentiation of induced pluripotent stem cells from EEC patients is rescued by APR-246/PRIMA-1MET. P.N.A.S 2012. . [2014-12-13]. （原始内容存档于2014-12-14）.

[18] Shiran MS, Tan GC, Sabariah AR, Rampal L, Phang KS. . The Medical Journal of Malaysia. Mar 2007, 62 (1): 36–9. PMID 17682568.

[19] Herawi M, Epstein JI. . The American Journal of Surgical Pathology. Jun 2007, 31 (6): 889–94. PMID 17527076. doi:10.1097/01.pas.0000213447.16526.7f.

[pmid15309021-20] Zhang H, Liu J, Cagle PT, Allen TC, Laga AC, Zander DS. . Modern Pathology. Jan 2005, 18 (1): 111–8. PMID 15309021. doi:10.1038/modpathol.3800251.

[pmid12692135-21] Fomenkov A, Huang YP, Topaloglu O, Brechman A, Osada M, Fomenkova T, Yuriditsky E, Trink B, Sidransky D, Ratovitski E. . The Journal of Biological Chemistry. Jun 2003, 278 (26): 23906–14. PMID 12692135. doi:10.1074/jbc.M300746200.

[pmid18311128-22] Yi R, Poy MN, Stoffel M, Fuchs E. . Nature. Mar 2008, 452 (7184): 225–9. PMID 18311128. doi:10.1038/nature06642.

[pmid18848452-23] Aberdam D, Candi E, Knight RA, Melino G. . Trends in Biochemical Sciences. Dec 2008, 33 (12): 583–91 [2017-11-13]. PMID 18848452. doi:10.1016/j.tibs.2008.09.002. （原始内容存档于2013-04-21）.