Viral transactivators specifically target distinct cellular protein kinases that phosphorylate the RNA polymerase II C-terminal domain.
Phosphorylation of the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II has been implicated as an important step in transcriptional regulation. Previously, we reported that a cellular CTD kinase, TAK, is targeted by the human immunodeficiency virus transactivator Tat. In the present study, we analyzed several other transactivators for the ability to interact with CTD kinases in vitro. The adenovirus E1A and herpes simplex virus VP16 proteins, but not other transactivators tested, were found to associate with a cellular kinase activity that hyperphosphorylates the CTD. The interaction is dependent upon a functional activation domain of E1A or VP16, suggesting that the interaction with a CTD kinase is relevant for the transactivation function of these proteins. The CTD kinase activities that interact with E1A and VP16 are related to each other but distinct from TAK. The Tat-, E1A- and VP16-associated CTD kinase activities detected in our assay also appear unrelated to MO15, the catalytic component of the CTD kinase activity of the general transcription factor TFIIH. Thus, this study has identified a novel interaction between viral transactivators and a cellular CTD kinase and suggests that at least two CTD kinases may mediate responses to viral transactivators.
Herrmann
C H
CH
Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA.
Gold
M O
MO
Rice
A P
AP
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D001483:Base Sequence; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D015534:Trans-Activators; D011494:Protein Kinases; D012319:RNA Polymerase II