P63

P63
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	4A9Z、1RG6、2RMN、2Y9T、2Y9U、3QYM、3QYN、3US0、3US1、3US2、3ZY0、3ZY1
识别号
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
相关疾病
	肺腺癌、lymphoblastic leukemia、肺癌、ADULT综合征、附肢-乳腺综合征、AEC综合征、split hand-foot malformation 2[1]
基因位置（人类）
染色体	3号染色体[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
基因本体
分子功能	• DNA-binding transcription activator activity, RNA polymerase II-specific; • 金属离子结合; • 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;
细胞组分	• 细胞质; • neuron projection; • 细胞核; • 粗面内质网; • 转录调节复合物; • 核质; • 树突; • 线粒体; • 高尔基体; • 细胞质基质; • 大分子复合体;
生物学过程	• 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; • 细胞增殖; • 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
	维基数据

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

.
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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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.
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.
Skipper M. . Nature Reviews Molecular Cell Biology. January 2007, 8 (1): 4–5. doi:10.1038/nrm2091.
Crum CP, McKeon FD. . Annual Review of Pathology. 2010, 5: 349–71. PMID 20078223. doi:10.1146/annurev-pathol-121808-102117.
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.
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）.
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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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拓展阅读

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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）.