Suppression of adenovirus E1A-induced apoptosis by mutated p53 is overcome by coexpression with Id proteins.
The rat 3Y1 derivative cell lines, EId10 and EId23, established by introducing the adenovirus E1A12S, Id-1H, and Id-2H cDNAs linked to the hormone-inducible promoter, express these proteins upon treatment with dexamethasone and elicit apoptosis, although these cell lines express mutated p53. The E1A mutants containing a deletion in either the N terminus or the conserved region 1 were unable to induce apoptosis in cooperation with Ids. Western blot analysis of the immunoprecipitates prepared from the dexamethasone-treated EId10 cell extract showed that Id-2H preferentially binds to E1A and E2A (E12/E47) helix-loop-helix transcription factors in vivo, but scarcely to the retinoblastoma protein. After induction of E1A and Ids, EId10 and EId23 cells began to accumulate in S phase and undergo apoptosis before entering G2 phase, suggesting that abnormal synthesis of DNA induced by coexpression of E1A, Id-1H, and Id-2H results in the induction of apoptosis. Apoptosis also is induced in mouse A40 (p53-/-) cells by E1A alone or E1A plus Ids after transient transfection of the expression vectors. The induction of apoptosis is stimulated by coexpression with wild-type p53; however, apoptosis induced by E1A alone was suppressed completely by coexpression with mutated p53, whereas apoptosis induced by E1A plus Ids was stimulated by the mutated p53 as done by wild-type p53. These results suggest that the suppressive function of mutated p53 is overcome by Ids.
Nakajima
T
T
Department of Biological Science and Technology, Science University of Tokyo, Noda-shi, Chiba 278, Japan.
Yageta
M
M
Shiotsu
K
K
Morita
K
K
Suzuki
M
M
Tomooka
Y
Y
Oda
K
K
D017500:Adenovirus E1A Proteins / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D018257:Helix-Loop-Helix Motifs; D051798:Inhibitor of Differentiation Protein 1; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D012097:Repressor Proteins; D016196:S Phase; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D017500:Adenovirus E1A Proteins; C497454:ID1 protein, rat; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D003907:Dexamethasone