Trp63

Summary

Gene Symbol: Trp63
Description: transformation related protein 63
Alias: AI462811, Ket, P51/P63, P63, P73l, Tp63, Trp53rp1, tumor protein 63
Species: mouse
Products:     Trp63

Top Publications

  1. Coutandin D, Lohr F, Niesen F, Ikeya T, Weber T, Schafer B, et al. Conformational stability and activity of p73 require a second helix in the tetramerization domain. Cell Death Differ. 2009;16:1582-9 pubmed publisher
    p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells...
  2. Rufini A, Weil M, McKeon F, Barlattani A, Melino G, Candi E. p63 protein is essential for the embryonic development of vibrissae and teeth. Biochem Biophys Res Commun. 2006;340:737-41 pubmed
    ..One of the genes involved in this process is p63, a member of the p53 family of transcription factors, essential for ectodermal development, as elucidated by the ..
  3. Hatsell S, Cowin P. Gli3-mediated repression of Hedgehog targets is required for normal mammary development. Development. 2006;133:3661-70 pubmed
    ..Thus, positive Hedgehog signaling is absent throughout mammary development, distinguishing the mammary gland from other epidermal appendages, such as hair follicles, which require Hedgehog pathway activity. ..
  4. McDade S, Henry A, Pivato G, Kozarewa I, Mitsopoulos C, Fenwick K, et al. Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation. Nucleic Acids Res. 2012;40:7190-206 pubmed publisher
    The p63 transcription factor (TP63) is critical in development, growth and differentiation of stratifying epithelia...
  5. Pignon J, Grisanzio C, Geng Y, Song J, Shivdasani R, Signoretti S. p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc Natl Acad Sci U S A. 2013;110:8105-10 pubmed publisher
    The tumor protein p63 (p63), and more specifically the NH2-terminal truncated (?N) p63 isoform, is a marker of basal epithelial cells and is required for normal development of several epithelial tissues, including the bladder and ..
  6. Marinari B, Ballaro C, Koster M, Giustizieri M, Moretti F, Crosti F, et al. IKKalpha is a p63 transcriptional target involved in the pathogenesis of ectodermal dysplasias. J Invest Dermatol. 2009;129:60-9 pubmed publisher
    The transcription factor p63 plays a pivotal role in the development and differentiation of the epidermis and epithelial appendages...
  7. Adorno M, Cordenonsi M, Montagner M, Dupont S, Wong C, Hann B, et al. A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell. 2009;137:87-98 pubmed publisher
    ..we show that TGFbeta-dependent cell migration, invasion and metastasis are empowered by mutant-p53 and opposed by p63. Mechanistically, TGFbeta acts in concert with oncogenic Ras and mutant-p53 to induce the assembly of a mutant-p53/..
  8. Alexandrova E, Petrenko O, Nemajerova A, Romano R, Sinha S, Moll U. ?Np63 regulates select routes of reprogramming via multiple mechanisms. Cell Death Differ. 2013;20:1698-708 pubmed publisher
    ..enhances reprogramming, revealing p53's barrier function for induced pluripotency, but the role of its homologs p63 and p73 are unknown. Here we report that in stark contrast to p53, p73 has no role in reprogramming...
  9. Goss A, Tian Y, Tsukiyama T, Cohen E, Zhou D, Lu M, et al. Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut. Dev Cell. 2009;17:290-8 pubmed publisher
    ..Together, these data reveal that canonical Wnt2/2b signaling is required for the specification of lung endoderm progenitors in the developing foregut...

More Information

Publications62

  1. Yi R, Poy M, Stoffel M, Fuchs E. A skin microRNA promotes differentiation by repressing 'stemness'. Nature. 2008;452:225-9 pubmed publisher
    ..We identify p63 as one of the conserved targets of miR-203 across vertebrates...
  2. Senoo M, Pinto F, Crum C, McKeon F. p63 Is essential for the proliferative potential of stem cells in stratified epithelia. Cell. 2007;129:523-36 pubmed
    ..Here we analyze p63, a gene whose deletion in mice results in the catastrophic loss of all stratified epithelia...
  3. Romano R, Birkaya B, Sinha S. A functional enhancer of keratin14 is a direct transcriptional target of deltaNp63. J Invest Dermatol. 2007;127:1175-86 pubmed
    ..Finally, we show that ectopic expression of either p63 isoform (deltaN or TA) can induce de novo expression of K14...
  4. Blanpain C, Lowry W, Pasolli H, Fuchs E. Canonical notch signaling functions as a commitment switch in the epidermal lineage. Genes Dev. 2006;20:3022-35 pubmed
  5. Ingraham C, Kinoshita A, Kondo S, Yang B, Sajan S, Trout K, et al. Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet. 2006;38:1335-40 pubmed
    ..Histological and gene expression analyses indicate that the primary defect is in keratinocyte differentiation and proliferation. This study describes a new role for an IRF family member in epidermal development. ..
  6. De Rosa L, Antonini D, Ferone G, Russo M, Yu P, Han R, et al. p63 Suppresses non-epidermal lineage markers in a bone morphogenetic protein-dependent manner via repression of Smad7. J Biol Chem. 2009;284:30574-82 pubmed publisher
    b>p63, a p53 family member, plays an essential role in epidermal development by regulating its transcriptional program...
  7. Candi E, Rufini A, Terrinoni A, Dinsdale D, Ranalli M, Paradisi A, et al. Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ. 2006;13:1037-47 pubmed
    Epidermal development requires the transcription factor p63, as p63-/- mice are born dead, without skin...
  8. Schmale H, Bamberger C. A novel protein with strong homology to the tumor suppressor p53. Oncogene. 1997;15:1363-7 pubmed
    ..The new KET protein is the first mammalian protein with strong homology to p53 in all evolutionary conserved regions...
  9. Flores E, Sengupta S, Miller J, Newman J, Bronson R, Crowley D, et al. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell. 2005;7:363-73 pubmed
    b>p63 and p73 are functionally and structurally related to the tumor suppressor p53. However, their own role in tumor suppression is unclear...
  10. Osada M, Nagakawa Y, Park H, Yamashita K, Wu G, Kim M, et al. p63-specific activation of the BPAG-1e promoter. J Invest Dermatol. 2005;125:52-60 pubmed
    b>p63, a member of the p53 superfamily, is an essential cell fate determinant for stratified epithelium...
  11. Gonfloni S, Di Tella L, Caldarola S, Cannata S, Klinger F, Di Bartolomeo C, et al. Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death. Nat Med. 2009;15:1179-85 pubmed publisher
    ..Such modifications affect p63 stability and induce a p63-dependent activation of proapoptotic promoters...
  12. Bell S, Schreiner C, Waclaw R, Campbell K, Potter S, Scott W. Sp8 is crucial for limb outgrowth and neuropore closure. Proc Natl Acad Sci U S A. 2003;100:12195-200 pubmed
    ..These observations indicate that Sp8 functions downstream of Wnt3, Fgf10, and Bmpr1a in the signaling cascade that mediates AER formation. ..
  13. Westfall M, Pietenpol J. p63: Molecular complexity in development and cancer. Carcinogenesis. 2004;25:857-64 pubmed
    Discovery of the p53 homologs p63 and p73 has brought new excitement to the p53 field...
  14. Hernández Acosta N, Cabrera Socorro A, Morlans M, Delgado F, Suárez Solá M, Sottocornola R, et al. Dynamic expression of the p53 family members p63 and p73 in the mouse and human telencephalon during development and in adulthood. Brain Res. 2011;1372:29-40 pubmed publisher
    b>p63 and p73, family members of the tumor suppressor p53, are critically involved in the life and death of mammalian cells. They display high homology and may act in concert...
  15. Leonard M, Kommagani R, Payal V, Mayo L, Shamma H, Kadakia M. ?Np63? regulates keratinocyte proliferation by controlling PTEN expression and localization. Cell Death Differ. 2011;18:1924-33 pubmed publisher
    ..of Akt activation by phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and the presence of putative p63-binding sites in the pten promoter led us to investigate whether ?Np63? regulates PTEN expression...
  16. Liu B, Liu Y, Du Y, Mardaryev A, Yang W, Chen H, et al. Cbx4 regulates the proliferation of thymic epithelial cells and thymus function. Development. 2013;140:780-8 pubmed publisher
    ..Furthermore, we show that Cbx4 physically interacts and functionally correlates with p63, which is a transcriptional regulator that is proposed to be important for the maintenance of the stemness of ..
  17. Kusakabe T, Hoshi N, Kimura S. Origin of the ultimobranchial body cyst: T/ebp/Nkx2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid. Dev Dyn. 2006;235:1300-9 pubmed
    ..1 and the other expressing p63. The former cell type, accounting for a majority of the UBB, requires T/ebp/Nkx2.1 for their survival...
  18. Murray Zmijewski F, Lane D, Bourdon J. p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Differ. 2006;13:962-72 pubmed
    b>p63, p73 and p53 compose a family of transcription factors involved in cell response to stress and development...
  19. Suh E, Yang A, Kettenbach A, Bamberger C, Michaelis A, Zhu Z, et al. p63 protects the female germ line during meiotic arrest. Nature. 2006;444:624-8 pubmed
    ..Here we show that the p53 homologue p63 (refs 5, 6), and specifically the TAp63 isoform, is constitutively expressed in female germ cells during meiotic ..
  20. Chikh A, Matin R, Senatore V, Hufbauer M, Lavery D, Raimondi C, et al. iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia. EMBO J. 2011;30:4261-73 pubmed publisher
    ..a novel autoregulatory feedback loop which controls crucial physiological activities by linking iASPP to p63, via two previously unreported microRNAs, miR-574-3p and miR-720...
  21. Koster M, Kim S, Huang J, Williams T, Roop D. TAp63alpha induces AP-2gamma as an early event in epidermal morphogenesis. Dev Biol. 2006;289:253-61 pubmed
    ..Our data identify AP-2gamma as the first in vivo target gene of TAp63alpha, and provide novel insights into the molecular mechanisms associated with early events in epidermal morphogenesis. ..
  22. Carroll D, Carroll J, Leong C, Cheng F, Brown M, Mills A, et al. p63 regulates an adhesion programme and cell survival in epithelial cells. Nat Cell Biol. 2006;8:551-61 pubmed
    b>p63 is critical for epithelial development yet little is known about the transcriptional programmes it regulates...
  23. Ihrie R, Marques M, Nguyen B, Horner J, Papazoglu C, Bronson R, et al. Perp is a p63-regulated gene essential for epithelial integrity. Cell. 2005;120:843-56 pubmed
    b>p63 is a master regulator of stratified epithelial development that is both necessary and sufficient for specifying this multifaceted program...
  24. Lo Iacono N, Mantero S, Chiarelli A, Garcia E, Mills A, Morasso M, et al. Regulation of Dlx5 and Dlx6 gene expression by p63 is involved in EEC and SHFM congenital limb defects. Development. 2008;135:1377-88 pubmed publisher
    ..SHFM-IV and Ectrodactyly-Ectodermal dysplasia-Cleft lip (EEC) are caused by mutations in p63, an ectoderm-specific p53-related transcription factor...
  25. Ferretti E, Li B, Zewdu R, Wells V, Hebert J, Karner C, et al. A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. Dev Cell. 2011;21:627-41 pubmed publisher
    ..Mutations of WNT, P63, and IRF6 yield CL/P in humans and mice; however, how these genes are regulated remains elusive...
  26. Lena A, Shalom Feuerstein R, Rivetti di Val Cervo P, Aberdam D, Knight R, Melino G, et al. miR-203 represses 'stemness' by repressing DeltaNp63. Cell Death Differ. 2008;15:1187-95 pubmed publisher
    ..The epidermis develops depending on the transcription factor p63, a member of the p53 family of transcription factors...
  27. Ferone G, Mollo M, Thomason H, Antonini D, Zhou H, Ambrosio R, et al. p63 control of desmosome gene expression and adhesion is compromised in AEC syndrome. Hum Mol Genet. 2013;22:531-43 pubmed publisher
    ..defects, cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder caused by mutations in the p63 gene, essential for embryonic development of stratified epithelia...
  28. Lopez R, Garcia Silva S, Moore S, Bereshchenko O, Martinez Cruz A, Ermakova O, et al. C/EBPalpha and beta couple interfollicular keratinocyte proliferation arrest to commitment and terminal differentiation. Nat Cell Biol. 2009;11:1181-90 pubmed publisher
    ..C/EBPs, therefore, couple basal keratinocyte cell cycle exit to commitment to differentiation through E2F repression and DNA binding, respectively, and may act to restrict the epidermal stem cell compartment. ..
  29. Mills A, Qi Y, Bradley A. Conditional inactivation of p63 by Cre-mediated excision. Genesis. 2002;32:138-41 pubmed
  30. Su X, Chakravarti D, Cho M, Liu L, Gi Y, Lin Y, et al. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature. 2010;467:986-90 pubmed publisher
  31. Romano R, Birkaya B, Sinha S. Defining the regulatory elements in the proximal promoter of DeltaNp63 in keratinocytes: Potential roles for Sp1/Sp3, NF-Y, and p63. J Invest Dermatol. 2006;126:1469-79 pubmed
    b>p63, a homolog of the tumor suppressor p53, plays an important role in the formation of stratified epithelium such as those in the epidermis of the skin...
  32. Kurita T, Cunha G, Robboy S, Mills A, Medina R. Differential expression of p63 isoforms in female reproductive organs. Mech Dev. 2005;122:1043-55 pubmed
    b>p63 is the identity switch for uterine/vaginal epithelial cell fate, and disruption of p63 expression by diethylstilbestrol (DES) induces cervical/vaginal adenosis in mice...
  33. King K, Ponnamperuma R, Gerdes M, Tokino T, Yamashita T, Baker C, et al. Unique domain functions of p63 isotypes that differentially regulate distinct aspects of epidermal homeostasis. Carcinogenesis. 2006;27:53-63 pubmed
    b>p63 is critical for squamous development and exists as multiple isotypes of two subclasses, TA and DeltaN. DeltaNp63 isotypes can antagonize transcription by TAp63 and p53, and are highly expressed in squamous cell cancers...
  34. Volckaert T, Campbell A, Dill E, Li C, Minoo P, De Langhe S. Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors. Development. 2013;140:3731-42 pubmed publisher
    ..Interestingly, our data presented here show that once epithelial cells are committed to the Sox2-positive airway epithelial cell fate, Fgf10 prevents ciliated cell differentiation and promotes basal cell differentiation. ..
  35. Restivo G, Nguyen B, Dziunycz P, Ristorcelli E, Ryan R, Özuysal Ö, et al. IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes. EMBO J. 2011;30:4571-85 pubmed publisher
    ..Thus, IRF6 is a primary Notch target in keratinocytes, which contributes to the role of this pathway in differentiation and tumour suppression. ..
  36. Augustin M, Bamberger C, Paul D, Schmale H. Cloning and chromosomal mapping of the human p53-related KET gene to chromosome 3q27 and its murine homolog Ket to mouse chromosome 16. Mamm Genome. 1998;9:899-902 pubmed
    b>KET is a member of the newly discovered family of proteins that is related to the tumor suppressor p53. Here we describe the molecular cloning of a human cDNA of 4846 bp encoding a protein of 680 amino acids...
  37. DeYoung M, Johannessen C, Leong C, Faquin W, Rocco J, Ellisen L. Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma. Cancer Res. 2006;66:9362-8 pubmed
    b>p63 is essential for normal epithelial development and is overexpressed in the vast majority of squamous cell carcinomas (SCC)...
  38. Su X, Cho M, Gi Y, Ayanga B, Sherr C, Flores E. Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and Arf. EMBO J. 2009;28:1904-15 pubmed publisher
    Mice lacking p63 cannot form skin, exhibit craniofacial and skeletal defects, and die soon after birth...
  39. Su X, Chakravarti D, Flores E. p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis. Nat Rev Cancer. 2013;13:136-43 pubmed publisher
    The role of p63 in cancer has been an area of intense debate and controversy. Is TP63 (which encodes p63) a tumour suppressor gene or an oncogene? This debate is partly due to the complexity of the gene...
  40. Sommer M, Poliak N, Upadhyay S, Ratovitski E, Nelkin B, Donehower L, et al. DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell Cycle. 2006;5:2005-11 pubmed
    b>p63 is highly expressed in the skin and appears to be an early marker of keratinocyte differentiation. To examine the role of p63 in vivo, we generated transgenic mice that overexpress deltaNp63alpha in the skin...
  41. Martinez P, Flores J, Blasco M. 53BP1 deficiency combined with telomere dysfunction activates ATR-dependent DNA damage response. J Cell Biol. 2012;197:283-300 pubmed publisher
    ..In intact mice, combined 53BP1/TRF1 deficiency in stratified epithelia resulted in earlier onset of DNA damage and increased CHK1 phosphorylation during embryonic development, leading to aggravation of skin phenotypes. ..
  42. Radoja N, Guerrini L, Lo Iacono N, Merlo G, Costanzo A, Weinberg W, et al. Homeobox gene Dlx3 is regulated by p63 during ectoderm development: relevance in the pathogenesis of ectodermal dysplasias. Development. 2007;134:13-8 pubmed
    ..Dlx3 and p63 act as part of the transcriptional regulatory pathways relevant in ectoderm derivatives, and autosomal mutations in ..
  43. Karni Schmidt O, Castillo Martin M, Shen T, Huaishen T, Gladoun N, Domingo Domenech J, et al. Distinct expression profiles of p63 variants during urothelial development and bladder cancer progression. Am J Pathol. 2011;178:1350-60 pubmed publisher
    The TP63 gene, a member of the TP53 tumor suppressor gene family, can be expressed as at least six isoforms due to alternative promoter use and alternative splicing...
  44. Yalcin Ozuysal O, Fiche M, Guitierrez M, Wagner K, Raffoul W, Brisken C. Antagonistic roles of Notch and p63 in controlling mammary epithelial cell fates. Cell Death Differ. 2010;17:1600-12 pubmed publisher
    ..The p53 homolog, p63, is required for the formation of mammary buds, but its function in the breast after birth is unknown...
  45. Candi E, Terrinoni A, Rufini A, Chikh A, Lena A, Suzuki Y, et al. p63 is upstream of IKK alpha in epidermal development. J Cell Sci. 2006;119:4617-22 pubmed
    ..The mouse Trp63 gene contains two promoters, driving the production of distinct proteins, one with an N-terminal trans-activation ..
  46. Candi E, Rufini A, Terrinoni A, Giamboi Miraglia A, Lena A, Mantovani R, et al. DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proc Natl Acad Sci U S A. 2007;104:11999-2004 pubmed
    b>p63, a homologue of the tumor suppressor p53, is pivotal for epithelial development, because its loss causes severe epithelial dysgenesis, although no information is so far available on the role of p63 in the thymus...
  47. Kameda Y, Ito M, Nishimaki T, Gotoh N. FRS2alpha is required for the separation, migration, and survival of pharyngeal-endoderm derived organs including thyroid, ultimobranchial body, parathyroid, and thymus. Dev Dyn. 2009;238:503-13 pubmed publisher
    ..for the thyroid lobe; parathormone (PTH), chromogranin A, P75(NTR), and S100 protein for the parathyroid gland; and p63 for the thymus) were normally expressed in the mutant tissues...
  48. Barbieri C, Pietenpol J. p63 and epithelial biology. Exp Cell Res. 2006;312:695-706 pubmed
    The transcription factor p63 is a homologue of the tumor suppressor p53...
  49. Perez Losada J, Wu D, DelRosario R, Balmain A, Mao J. p63 and p73 do not contribute to p53-mediated lymphoma suppressor activity in vivo. Oncogene. 2005;24:5521-4 pubmed
    p53 is one of the most important tumor suppressor genes in human cancer, but the roles of its homologues p63 and p73 in tumor suppression, alone or in collaboration with p53, remains controversial...
  50. Kurita T, Medina R, Mills A, Cunha G. Role of p63 and basal cells in the prostate. Development. 2004;131:4955-64 pubmed
    ..Urogenital sinus (UGS) isolated from p63(+/+) and p63(-/-) embryos developed into prostate when grafted into adult male nude mice...
  51. Kurata S, Okuyama T, Osada M, Watanabe T, Tomimori Y, Sato S, et al. p51/p63 Controls subunit alpha3 of the major epidermis integrin anchoring the stem cells to the niche. J Biol Chem. 2004;279:50069-77 pubmed
    p51/p63, a member of the tumor suppressor p53 gene family, is crucial for skin development...
  52. Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson R, et al. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature. 1999;398:714-8 pubmed
    The p63 gene, a homologue of the tumour-suppressor p53, is highly expressed in the basal or progenitor layers of many epithelial tissues...
  53. BURNLEY P, Rahman M, Wang H, Zhang Z, Sun X, Zhuge Q, et al. Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging. Cell Death Dis. 2013;4:e932 pubmed publisher
    The p63 gene regulates thymic epithelial cell (TEC) proliferation, whereas FoxN1 regulates their differentiation. However, their collaborative role in the regulation of TEC homeostasis during thymic aging is largely unknown...