Новая немецкая медицина. Советы от немецкая медицина. Клиника немецкой семейной медицины. Почему в израиле хорошая медицина. Главные новости медицины израиля. Медицина в израиле отзывы. Аденома простаты лечение. Быстрое народное лечение аденомы простаты. Аденома простаты и простатит. Легкий способ перестать курить. Как перестать курить уже сегодня. Как перестать хотеть курить. Уход за кожей лица. Качественный уход за кожей летом. Домашний уход за кожей. Боли на ранних сроках беременности. Быстрое лечение на ранних сроках беременности. Ощущения на ранних сроках беременности. Воспаленные гланды лечение. Чем лечить воспаленные гланды дома. Воспаленные гланды симптомы. Прыщи на лице как избавиться. Как навсегда избавиться от прыщей с лица. Прыщи на подбородке как избавиться.

p63, a Story of Mice and Men

Hans Vanbokhoven, Gerry Melino, Eleonora Candi and Wim Declercq


Journal of Investigative Dermatology (2011), Volume 131 1196-1207


Читать статью


The transcription factor p63 is essential for the formation of the epidermis and other stratifying epithelia. This is clearly demonstrated by the severe abnormality of p63-deficient mice and by the development of certain types of ectodermal dysplasias in humans as a result of p63 mutations. Investigation of the in vivo functions of p63 is complicated by the occurrence of 10 different splicing isoforms and by its interaction with the other family members, p53 and p73. In vitro and in vivo models have been used to unravel the functions of p63 and its different isoforms, but the results or their interpretation are often contradictory. This review focuses on what mammalian in vivo models and patient studies have taught us in the last 10 years.


Acampora D, Merlo GR, Paleari L et al. (1999) Craniofacial, vestibular and bone defects in mice lacking the distal-less-related gene Dlx5. Development 126:3795–809

Adorno M, Cordenonsi M, Montagner M et al. (2009) A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell 137:87–98

Amiel J, Bougeard G, Francannet C et al. (2001) TP63 gene mutation in ADULT syndrome. Eur J Hum Genet 9:642–5

Beaty TH, Murray JC, Marazita ML et al. (2010) A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat Genet 42:525–9

Bertola DR, Kim CA, Albano LM et al. (2004) Molecular evidence that AEC syndrome and Rapp-Hodgkin syndrome are variable expression of a single genetic disorder. Clin Genet 66:79–80

Birkaya B, Ortt K, Sinha S (2007) Novel in vivo targets of DeltaNp63 in keratinocytes identified by a modified chromatin immunoprecipitation approach. BMC Mol Biol 8:43

Blanpain C, Fuchs E (2009) Epidermal homeostasis: a balancing act of stem cells in the skin. Nat Rev Mol Cell Biol 10:207–17

Bourdon JC (2007) p53 Family isoforms. Curr Pharm Biotechnol 8:332–6

Candi E, Dinsdale D, Rufini A et al. (2007a) TAp63 and DeltaNp63 in cancer and epidermal development. Cell Cycle 6:274–85

Candi E, Rufini A, Terrinoni A et al. (2006a) Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ 13:1037–47

Candi E, Rufini A, Terrinoni A et al. (2007b) DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proc Natl Acad Sci USA 104:11999–2004

Candi E, Terrinoni A, Rufini A et al. (2006b) p63 is upstream of IKK alpha in epidermal development. J Cell Sci 119:4617–22

Capdevila J, Izpisua Belmonte JC (2001) Patterning mechanisms controlling vertebrate limb development. Annu Rev Cell Dev Biol 17:87–132

Carroll DK, Carroll JS, Leong CO et al. (2006) p63 regulates an adhesion programme and cell survival in epithelial cells. Nat Cell Biol 8:551–61

Celli J, Duijf P, Hamel BC et al. (1999) Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell 99:143–53

Cheng W, Jacobs WB, Zhang JJ et al. (2006) DeltaNp63 plays an anti-apoptotic role in ventral bladder development. Development 133:4783–92

Chikh A, Sayan E, Thibaut S et al. (2007) Expression of GATA-3 in epidermis and hair follicle: relationship to p63. Biochem Biophys Res Commun 361:1–6

Chitayat D, Babul R, Silver MM et al. (1996) Terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27-qter)]. Am J Med Genet 61:45–8

Cho MS, Chan IL, Flores ER (2010) DeltaNp63 transcriptionally regulates brachyury, a gene with diverse roles in limb development, tumorigenesis and metastasis. Cell Cycle 9: 2434–41

Clements SE, Techanukul T, Holden ST et al. (2010) Rapp-Hodgkin and Hay-Wells ectodermal dysplasia syndromes represent a variable spectrum of the same genetic disorder. Br J Dermatol 163:624–9

Collavin L, Lunardi A, Del Sal G (2010) p53- family proteins and their regulators: hubs and spokes in tumor suppression. Cell Death Differ 17:901–11

Crum CP, McKeon FD (2010) p63 in epithelial survival, germ cell surveillance, and neoplasia. Annu Rev Pathol 5:349–71

de Biase D, Morandi L, Degli Esposti R et al. (2010) p63 short isoforms are found in invasive carcinomas only and not in benign breast conditions. Virchows Arch 456:395–401

de Guzman Strong C, Wertz PW, Wang C et al. (2006) Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3. J Cell Biol 175:661–70

de Mollerat XJ, Gurrieri F, Morgan CT et al. (2003) A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24. Hum Mol Genet 12:1959–71

Del Campo M, Jones MC, Veraksa AN et al. (1999) Monodactylous limbs and abnormal genitalia are associated with hemizygosity for the human 2q31 region that includes the HOXD cluster. Am J Hum Genet 65:104–10

Deyoung MP, Ellisen LW (2007) p63 and p73 in human cancer: defining the network. Oncogene 26:5169–83

Dianzani I, Garelli E, Gustavsson P et al. (2003) Rapp-Hodgkin and AEC syndromes due to a new frameshift mutation in the TP63 gene. J Med Genet 40:e133

Dohn M, Zhang S, Chen X (2001) p63alpha and DeltaNp63alpha can induce cell cycle arrest and apoptosis and differentially regulate p53 target genes. Oncogene 20:3193–205

Duijf PH, van Bokhoven H, Brunner HG (2003) Pathogenesis of split-hand/split-foot malformation. Hum Mol Genet 12 Spec No 1:R51–60

Duijf PH, Vanmolkot KR, Propping P et al. (2002) Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Hum Mol Genet 11:799–804

Faiyaz-Ul-Haque M, Zaidi SH, King LM et al. (2005) Fine mapping of the X-linked splithand/ split-foot malformation (SHFM2) locus to a 5.1-Mb region on Xq26.3 and analysis of candidate genes. Clin Genet 67:93–7

Flores ER (2007) The roles of p63 in cancer. Cell Cycle 6:300–4

Flores ER, Sengupta S, Miller JB et al. (2005) Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 7:363–73

Ghioni P, Bolognese F, Duijf PH et al. (2002) Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains. Mol Cell Biol 22:8659–68

Gonfloni S, Di Tella L, Caldarola S et al. (2009) Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapyinduced death. Nat Med 15:1179–85

Gressner O, Schilling T, Lorenz K et al. (2005) TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria. EMBO J 24:2458–71

Gritli-Linde A (2010) p63 and IRF6: brothers in arms against cleft palate. J Clin Invest 120:1386–9

Guo X, Keyes WM, Papazoglu C et al. (2009) TAp63 induces senescence and suppresses tumorigenesis in vivo. Nat Cell Biol 11:1451–7

Helton ES, Zhu J, Chen X (2006) The unique NH2-terminally deleted (DeltaN) residues, the PXXP motif, and the PPXY motif are required for the transcriptional activity of the DeltaN variant of p63. J Biol Chem 281:2533–42

Hu Y, Baud V, Delhase M et al. (1999) Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase. Science 284:316–20

Hu Y, Baud V, Oga T et al. (2001) IKKalpha controls formation of the epidermis independently of NF-kappaB. Nature 410:710–4

Ianakiev P, Kilpatrick MW, Toudjarska I et al. (2000) Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27. Am J Hum Genet 67:59–66

Ihrie RA, Marques MR, Nguyen BT et al. (2005) Perp is a p63-regulated gene essential for epithelial integrity. Cell 120:843–56

Indelman M, Bergman R, Lurie R et al. (2002) A missense mutation in CDH3, encoding Pcadherin, causes hypotrichosis with juvenile macular dystrophy. J Invest Dermatol 119:1210–3

Itin PH (2009) Rationale and background as basis for a new classification of the ectodermal dysplasias. Am J Med Genet A 149A:1973–6

Kannu P, Savarirayan R, Ozoemena L et al. (2006) Rapp-Hodgkin ectodermal dysplasia syndrome: the clinical and molecular overlap with Hay-Wells syndrome. Am J Med Genet A 140:887–91

Kantaputra PN, Hamada T, Kumchai T et al. (2003) Heterozygous mutation in the SAM domain of p63 underlies Rapp-Hodgkin ectodermal dysplasia. J Dent Res 82:433–7

Kaufman CK, Zhou P, Pasolli HA et al. (2003) GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev 17:2108–22

Keyes WM, Vogel H, Koster MI et al. (2006) p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors. Proc Natl Acad Sci USA 103:8435–40

Keyes WM, Wu Y, Vogel H et al. (2005) p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev 19:1986–99

Kjaer KW, Hansen L, Schwabe GC et al. (2005) Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome). J Med Genet 42:292–8

Kondo S, Schutte BC, Richardson RJ et al. (2002) Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet 32:285–9

Koster MI, Dai D, Marinari B et al. (2007a) p63 induces key target genes required for epidermal morphogenesis. Proc Natl Acad Sci USA 104:3255–60

Koster MI, Dai D, Roop DR (2007b) Conflicting roles for p63 in skin development and carcinogenesis. Cell Cycle 6:269–73

Koster MI, Kim S, Mills AA et al. (2004) p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev 18:126–31

Koster MI, Lu SL, White LD et al. (2006) Reactivation of developmentally expressed p63 isoforms predisposes to tumor development and progression. Cancer Res 66:3981–6

Koster MI, Marinari B, Payne AS et al. (2009) DeltaNp63 knockdown mice: A mouse model for AEC syndrome. Am J Med Genet A 149A:1942–7

Kouwenhoven EN, van Heeringen SJ, Tena JJ et al. (2010) Genome-wide profiling of p63 DNAbinding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus. PLoS Genet 6:e1001065

Kurata S, Okuyama T, Osada M et al. (2004) p51/p63 Controls subunit alpha3 of the major epidermis integrin anchoring the stem cells to the niche. J Biol Chem 279:50069–77

Kurita T, Cunha GR, Robboy SJ et al. (2005) Differential expression of p63 isoforms in female reproductive organs. Mech Dev 122:1043–55

Lang GA, Iwakuma T, Suh YA et al. (2004) Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell 119:861–72

Lena AM, Shalom-Feuerstein R, di Val Cervo PR et al. (2008) miR-203 represses ‘‘stemness’’ by repressing DeltaNp63. Cell Death Differ 15:1187–95

Leoyklang P, Siriwan P, Shotelersuk V (2006) A mutation of the p63 gene in non-syndromic cleft lip. J Med Genet 43:e28

Lin YL, Sengupta S, Gurdziel K et al. (2009) p63 and p73 transcriptionally regulate genes involved in DNA repair. PLoS Genet 5:e1000680

Liu C, Nakamura E, Knezevic V et al. (2003) A role for the mesenchymal T-box gene Brachyury in AER formation during limb development. Development 130:1327–37

Livera G, Petre-Lazar B, Guerquin MJ et al. (2008) p63 null mutation protects mouse oocytes from radio-induced apoptosis. Reproduction 135:3–12

Lo Iacono N, Mantero S, Chiarelli A et al. (2008) Regulation of Dlx5 and Dlx6 gene expression by p63 is involved in EEC and SHFM congenital limb defects. Development 135:1377–88

Mangiulli M, Valletti A, Caratozzolo MF et al. (2009) Identification and functional characterization of two new transcriptional variants of the human p63 gene. Nucleic Acids Res 37:6092–104

Marinari B, Ballaro C, Koster MI et al. (2009) IKKalpha is a p63 transcriptional target involved in the pathogenesis of ectodermal dysplasias. J Invest Dermatol 129:60–9

McGrath JA, Duijf PH, Doetsch V et al. (2001) Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63. Hum Mol Genet 10:221–9

Medawar A, Virolle T, Rostagno P et al. (2008) DeltaNp63 is essential for epidermal commitment of embryonic stem cells. PLoS ONE 3:e3441

Mikkola ML (2007) p63 in skin appendage development. Cell Cycle 6:285–90

Mikkola ML, Costanzo A, Thesleff I et al. (2010) Treasure or artifact: a decade of p63 research speaks for itself. Cell Death Differ 17:180–3; author reply 4–6

Mills AA, Qi Y, Bradley A (2002) Conditional inactivation of p63 by Cre-mediated excision. Genesis 32:138–41

Mills AA, Zheng B, Wang XJ et al. (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398:708–13

Moretti F, Marinari B, Lo Iacono N et al. (2010) A regulatory feedback loop involving p63 and IRF6 links the pathogenesis of 2 genetically different human ectodermal dysplasias. J Clin Invest 120:1570–7

Muller PA, Caswell PT, Doyle B et al. (2009) Mutant p53 drives invasion by promoting integrin recycling. Cell 139:1327–41

Ortt K, Sinha S (2006) Derivation of the consensus DNA-binding sequence for p63 reveals unique requirements that are distinct from p53. FEBS Lett 580:4544–50

Osada M, Park HL, Nagakawa Y et al. (2005) Differential recognition of response elements determines target gene specificity for p53 and p63. Mol Cell Biol 25:6077–89

Perez CA, Pietenpol JA (2007) Transcriptional programs regulated by p63 in normal epithelium and tumors. Cell Cycle 6:246–54

Pollazzon M, Grosso S, Papa FT et al. (2009) A 9.3Mb microdeletion of 3q27.3q29 associated with psychomotor and growth delay, tricuspid valve dysplasia and bifid thumb. Eur J Med Genet 52:131–3

Pozzi S, Zambelli F, Merico D et al. (2009) Transcriptional network of p63 in human keratinocytes. PLoS ONE 4:e5008

Proksch E, Brandner JM, Jensen JM (2008) The skin: an indispensable barrier. Exp Dermatol 17:1063–72

Rahimov F, Marazita ML, Visel A et al. (2008) Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nat Genet 40:1341–7

Rinne T, Bolat E, Meijer R et al. (2009) Spectrum of p63 mutations in a selected patient cohort affected with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). Am J Med Genet A 149A:1948–51

Rinne T, Brunner HG, van Bokhoven H (2007) p63-associated disorders. Cell Cycle 6:262–8

Rinne T, Spadoni E, Kjaer KW et al. (2006) Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene. Eur J Hum Genet 14:904–10

Robledo RF, Rajan L, Li X et al. (2002) The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev 16:1089–101

Romano RA, Birkaya B, Sinha S (2007) A functional enhancer of keratin14 is a direct transcriptional target of deltaNp63. J Invest Dermatol 127:1175–86

Romano RA, Ortt K, Birkaya B et al. (2009) An active role of the DeltaN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate. PLoS ONE 4:e5623

Romano RA, Smalley K, Liu S et al. (2010) Abnormal hair follicle development and altered cell fate of follicular keratinocytes in transgenic mice expressing DeltaNp63alpha. Development 137:1431–9

Scapoli L, Palmieri A, Martinelli M et al. (2005) Strong evidence of linkage disequilibrium between polymorphisms at the IRF6 locus and nonsyndromic cleft lip with or without cleft palate, in an Italian population. Am J Hum Genet 76:180–3

Scherer SW, Poorkaj P, Allen T et al. (1994) Fine mapping of the autosomal dominant split hand/split foot locus on chromosome 7, band q21.3-q22.1. Am J Hum Genet 55:12–20

Schilling T, Kairat A, Melino G et al. (2010) Interference with the p53 family network contributes to the gain of oncogenic function of mutant p53 in hepatocellular carcinoma. Biochem Biophys Res Commun 394:817–23

Senoo M, Pinto F, Crum CP et al. (2007) p63 Is essential for the proliferative potential of stem cells in stratified epithelia. Cell 129:523–36

Shimomura Y, Wajid M, Shapiro L et al. (2008) Pcadherin is a p63 target gene with a crucial role in the developing human limb bud and hair follicle. Development 135:743–53

Simeone A, Acampora D, Pannese M et al. (1994) Cloning and characterization of two members of the vertebrate Dlx gene family. Proc Natl Acad Sci USA 91:2250–4

Stehmeier P, Muller S (2009) Regulation of p53 family members by the ubiquitin-like SUMO system. DNA Repair (Amst) 8:491–8

Su X, Chakravarti D, Cho MS et al. (2010) TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 467:986–90

Su X, Cho MS, Gi YJ et al. (2009a) Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and Arf. EMBO J 28:1904–15

Su X, Paris M, Gi YJ et al. (2009b) TAp63 prevents premature aging by promoting adult stem cell maintenance. Cell Stem Cell 5:64–75

Suh EK, Yang A, Kettenbach A et al. (2006) p63 protects the female germ line during meiotic arrest. Nature 444:624–8

Testoni B, Borrelli S, Tenedini E et al. (2006) Identification of new p63 targets in human keratinocytes. Cell Cycle 5:2805–11

Thomason HA, Zhou H, Kouwenhoven EN et al. (2010) Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice. J Clin Invest 120:1561–9

Truong AB, Kretz M, Ridky TW et al. (2006) p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev 20:3185–97

Ugur SA, Tolun A (2008) Homozygous WNT10b mutation and complex inheritance in splithand/ foot malformation. Hum Mol Genet 17:2644–53

van Bokhoven H, Hamel BC, Bamshad M et al. (2001) p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation. Am J Hum Genet 69:481–92

Vigano MA, Lamartine J, Testoni B et al. (2006) New p63 targets in keratinocytes identified by a genome-wide approach. EMBO J 25:5105–16

Wolff S, Talos F, Palacios G et al. (2009) The alpha/beta carboxy-terminal domains of p63 are required for skin and limb development. New insights from the Brdm2 mouse which is not a complete p63 knockout but expresses p63 gamma-like proteins. Cell Death Differ 16:1108–17

Yang A, Schweitzer R, Sun D et al. (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398:714–8

Yang A, Zhu Z, Kapranov P et al. (2006) Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol Cell 24:593–602

Yi R, Poy MN, Stoffel M et al. (2008) A skin microRNA promotes differentiation by repressing ‘‘stemness’’. Nature 452:225–9

Zucchero TM, Cooper ME, Maher BS et al. (2004) Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate. N Engl J Med 351:769–80

Прочитано 3093 раз
Оцените материал
(0 голосов)
Опубликовано в СТАТЬИ
Авторизуйтесь, чтобы получить возможность оставлять комментарии


Управление научных исследований СПбГТИ (ТУ)

Горячие новости

Приборное оснащение лаборатории

Rambler's Top100
//'+ 'Рейтинг@Mail.ru<\/a><\/p>');})(window,navigator,document);//]]>