Down-regulation of p63 is required for epidermal UV-B-induced apoptosis.

Abstract:

:In the epidermis, p53 plays an important role in UV-B protection that led us to examine the role, if any, that p63, a p53 homologue highly expressed in the basal layer of the epidermis, might play in the epidermal UV-B response. One p63 isoform, deltaNp63alpha, decreased dramatically in normal keratinocytes or newborn epidermis at both the protein and RNA levels after UV-B irradiation. In an attempt to further investigate the significance of the UV-B-induced decrease of this p63 isoform as well as further delineate the function of p63 in the epidermis, we generated transgenic mice that constitutively express deltaNp63alpha in the mouse epidermis using the loricrin promoter (ML.deltaNp63alpha). The ML.deltaNp63alpha mouse epidermis developed normally, with no overt phenotype and an unaltered proliferation rate. When challenged by UV-B exposure, the ML.deltaNp63alpha mice exhibited a 40-45% decrease in the number of apoptotic cells in the epidermis as compared with nontransgenic littermates. These results suggest that aberrant expression of deltaNp63alpha altered the UV-B-induced apoptotic pathway in the transgenic epidermis, proving that down-regulation of deltaNp63alpha in response to UV-B is important to epidermal apoptosis. The forced overexpression of deltaNp63alpha may act via a dominant negative effect on the endogenous p53 transcriptional activity required for UV-B-induced apoptosis.

journal_name

Cancer Res

journal_title

Cancer research

authors

Liefer KM,Koster MI,Wang XJ,Yang A,McKeon F,Roop DR

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

4016-20

issue

15

eissn

0008-5472

issn

1538-7445

journal_volume

60

pub_type

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