WDR68 is essential for cellular proliferation induced by Adenovirus Type 5 E1A

Despite previous data suggesting that the adenovirus 5 E1A protein promotes quiescent cells entry into S-phase and stimulates cell proliferation, the precise mechanisms are still debated. Here, we demonstrate that WDR68, a highly conserved WD40-repeat protein, significantly promotes cell proliferation and activates the transcription of a large number of crucial genes in 293T cells alone, in accordance with E1A protein. Subsequently, co-immunoprecipitation assays showed that both E1A and WDR68 bind to the small pocket domain of RB, and the interaction between E1A and RB does not depend on WDR68, indicating that the above effect induced by WDR68 and E1A is not involved in RB. Moreover, knock down of CtBP2, DYRK1B and FOXK1 in 293T cells without WDR68 significantly stimulates transcription of a few representative genes. These results suggested that binding of E1A to WDR68 contributes it's sequestering transcription corepressors CtBP2, DYRK1B and FOXK1 and activates transcription of cell cycle-related genes. Collectively, these findings show that WDR68 plays a central factor in cell cycle progress-regulated by E1A and might be a potential therapeutic target for adenovirus infection and adenovirus-related tumors in future studies.