S-phase induction by adenovirus E1A requires activation of cdc25a tyrosine phosphatase.
Adenovirus E1A proteins can induce quiescent cells to enter S-phase and also affect the expression of cellular genes including various cell cycle regulators. Here we show that human cdc25A, a tyrosine phosphatase involved in regulation of the G1/S-phase transition of the cell cycle, is a target of the adenovirus E1A protein in virus-infected human fibroblasts. Expression of E1A in quiescent fibroblasts leads to a rapid increase in cdc25A phosphatase activity and also increases both cdc25A and cyclin E gene expression. Inhibition of cdc25A function by antibody injection prevents virus-induced entry into S-phase. These results indicate that induction of high levels of cdc25A and its potential positive regulator cyclin E mediates the ability of E1A to induce S-phase in the presence of antiproliferative signals.
Spitkovsky
D
D
Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Germany.
Jansen-Dürr
P
P
Karsenti
E
E
Hoffman
I
I
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D016196:S Phase / Q000235:genetics*; D020687:cdc25 Phosphatases
D017500:Adenovirus E1A Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases