p51A (TAp63 gamma), a p53 homolog, accumulates in response to DNA damage for cell regulation

p51A, or TAp63 gamma, a translation product of gene p51, or p63, was identi fied as a homolog of p53 in its primary structure and transactivating funct ion. p53 plays a decision-making role in inducing either cell cycle arrest or apoptosis in response to DNA damage, and thereby preserves genome integr ity of living cells, To compare the biological activities between p51A and p53, cell lines with low-level, constitutive expression of each protein wer e obtained by cDNA transfection of mouse erythroleukemic cells. Production of p51A with an apparent molecular mass of 57-kilodalton (kD) accompanied i nduction of p21(wafl) and appearance of hemoglobin-producing cells. After D NA-damaging treatment either with ultraviolet light (UV) irradiation or wit h actinomycin D, the p51A protein accumulated in time courses corresponding to those of wild-type p53, and caused an increase in the hemoglobin-positi ve cell count. In contrast, p53-accumulated cells underwent apoptosis witho ut exhibiting the feature of erythroid differentiation, The mode of p21(waf l) and Bax-alpha upregulations varied between p51A- and p53-expressing cell s and between the types of DNA damage. These results suggest the possibilit y that p51A induces differentiation under genotoxic circumstances. There ma y be cellular factors that control p51A protein stability and transactivati ng ability.