Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice
Eleonora Candi,Alessandro Rufini,Alessandro Terrinoni,David Dinsdale,Marco Ranalli,Andrea Paradisi,V De Laurenzi,Luigi Giusto Spagnoli,M V Catani,Safaa M. Ramadan,Richard A. Knight,Gerry Melino,Gerry Melino +12 more
TL;DR: The two p63 isoforms appear to play distinct cooperative roles in epidermal formation, as double TAp63α/ΔNp 63α complementation showed greater patches of differentiated skin and at the ultrastructural level, there was clear reformation of a distinct basal membrane and hemidesmosomes.
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Abstract: Epidermal development requires the transcription factor p63, as p63-/- mice are born dead, without skin. The gene expresses two proteins, one with an amino-terminal transactivation domain (TAp63) and one without (deltaNp63), although their relative contribution to epidermal development is unknown. To address this issue, we reintroduced TAp63alpha and/or deltaNp63alpha under the K5 promoter into p63-/- mice by in vivo genetic complementation. Whereas p63-/- and p63-/-;TA mice showed extremely rare patches of poorly differentiated keratinocytes, p63-/-;deltaN mice showed significant epidermal basal layer formation. Double TAp63alpha/deltaNp63alpha complementation showed greater patches of differentiated skin; at the ultrastructural level, there was clear reformation of a distinct basal membrane and hemidesmosomes. At the molecular level, deltaNp63 regulated expression of genes characteristic of the basal layer (K14), interacting (by Chip, luc assay) with the third p53 consensus site. Conversely, TAp63 transcribed the upper layer's genes (Ets-1, K1, transglutaminases, involucrin). Therefore, the two p63 isoforms appear to play distinct cooperative roles in epidermal formation.
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Citations
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References
p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development
Annie Yang,Ronen Schweitzer,Deqin Sun,Mourad Kaghad,Nancy Walker,Roderick T. Bronson,Clifford J. Tabin,Arlene H. Sharpe,Daniel Caput,Christopher P. Crum,Frank McKeon +10 more
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p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.
Annie Yang,Mourad Kaghad,Yunmei Wang,Emily Gillett,Mark D. Fleming,Mark D. Fleming,Mark D. Fleming,Volker Dötsch,Nancy C. Andrews,Nancy C. Andrews,Daniel Caput,Frank McKeon +11 more
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TL;DR: It is shown that basal epidermal cells use their polarity to divide asymmetrically, generating a committed suprabasal cell and a proliferative basal cell and it is demonstrated that integrins and cadherins are essential for the apical localization of atypical protein kinase C, the Par3–LGN–Inscuteable complex and NuMA–dynactin to align the spindle.
p63 and p73: p53 mimics, menaces and more
Annie Yang,Frank McKeon +1 more
TL;DR: Both oncogenic and tumour-suppressor properties have now been attributed to the p53 homologues, perhaps reflecting the complex, often contradictory, protein products encoded by these genes.
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