Modulation of p120E4F transcriptional activity by the Gam1 adenoviral early protein.
Gam1, an early adenoviral CELO protein, is required for viral replication. Consistent with its ability to inhibit histone deacetylation by HDAC1, Gam1 activates transcription. In this report, we identify the cellular transcription factor p120(E4F) as a Gam1 interaction partner. p120(E4F) is a low-abundance transcription factor that represses the adenovirus E4 promoter. Here we demonstrate that p120(E4F) interacts with HDAC1 in vivo and in vitro, and that E4F-mediated transcriptional repression is alleviated by the HDAC inhibitor trichostatin A or by overexpressing Gam1. A mutant E4 promoter unresponsive to E4F-mediated transcriptional repression is also not stimulated by Gam1. Moreover, our cofractionation experiments demonstrate that p120(E4F), HDAC1 and Gam1 may be concomitantly present in protein complexes. We conclude that Gam1 activates E4-dependent transcription possibly by inactivating HDAC1.
Department of Experimental Oncology, European Institute of Oncology, via Ripamonti, 435, 20141 Milan, Italy.
Riccardo
R
Colombo
Giulio F
GF
Draetta
Susanna
S
Chiocca
D000215:Acylation; D000256:Adenoviridae / Q000502:physiology*; D017504:Adenovirus E4 Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D011233:Precipitin Tests; D012097:Repressor Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics
D017504:Adenovirus E4 Proteins; C105052:CELO protein, adenovirus; D006657:Histones; D012097:Repressor Proteins; D014764:Viral Proteins; C411663:transcription factor p120(E4F); C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases