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Advances in Brief |
Departments of Molecular and Cellular Biology [K. M. L., X-J. W., D. R. R.] and Dermatology [X-J. W., D. R. R.] and Program in Developmental Biology [M. I. K., D. R. R], Baylor College of Medicine, Houston, Texas 77030, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115 [A. Y., F. M.]
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, 
Np63
, 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
Np63 in the mouse epidermis using the loricrin promoter
(ML.Np63). The ML.Np63 mouse epidermis developed normally,
with no overt phenotype and an unaltered proliferation rate. When
challenged by UV-B exposure, the ML.Np63 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 Np63 altered the UV-B-induced apoptotic
pathway in the transgenic epidermis, proving that down-regulation of
Np63 in response to UV-B is important to epidermal apoptosis. The
forced overexpression of Np63 may act via a dominant negative
effect on the endogenous p53 transcriptional activity required for
UV-B-induced apoptosis.
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P. Mrass, M. Rendl, M. Mildner, F. Gruber, B. Lengauer, C. Ballaun, L. Eckhart, and E. Tschachler Retinoic Acid Increases the Expression of p53 and Proapoptotic Caspases and Sensitizes Keratinocytes to Apoptosis: A Possible Explanation for Tumor Preventive Action of Retinoids Cancer Res., September 15, 2004; 64(18): 6542 - 6548. [Abstract] [Full Text] [PDF]
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P. P. Massion, P. M. Taflan, S. M. Jamshedur Rahman, P. Yildiz, Y. Shyr, M. E. Edgerton, M. D. Westfall, J. R. Roberts, J. A. Pietenpol, D. P. Carbone, et al. Significance of p63 Amplification and Overexpression in Lung Cancer Development and Prognosis Cancer Res., November 1, 2003; 63(21): 7113 - 7121. [Abstract] [Full Text] [PDF]
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E. E. H. Galindo, C. Theiss, K.-P. Steuhl, and D. Meller Expression of {Delta}Np63 in Response to Phorbol Ester in Human Limbal Epithelial Cells Expanded on Intact Human Amniotic Membrane Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 2959 - 2965. [Abstract] [Full Text] [PDF]
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M. D. Westfall, D. J. Mays, J. C. Sniezek, and J. A. Pietenpol The {Delta}Np63{alpha} Phosphoprotein Binds the p21 and 14-3-3{sigma} Promoters In Vivo and Has Transcriptional Repressor Activity That Is Reduced by Hay-Wells Syndrome-Derived Mutations Mol. Cell. Biol., April 1, 2003; 23(7): 2264 - 2276. [Abstract] [Full Text] [PDF]
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E. A. Ratovitski, M. Patturajan, K. Hibi, B. Trink, K. Yamaguchi, and D. Sidransky p53 associates with and targets Delta Np63 into a protein degradation pathway PNAS, February 13, 2001; 98(4): 1817 - 1822. [Abstract] [Full Text] [PDF]
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M. Tan, J. Bian, K. Guan, and Y. Sun p53CP is p51/p63, the third member of the p53 gene family: partial purification and characterization Carcinogenesis, February 1, 2001; 22(2): 295 - 300. [Abstract] [Full Text] [PDF]
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