Nuclear c-Abl is a COOH-terminal repeated domain (CTD)-tyrosine kinase-specific for the mammalian RNA polymerase II: Possible role in transcription elongation

The c-Abl tyrosine kinase has been shown to interact with the COOH-terminal repeated domain (CTD) of mammalian RNA polymerase II and can phosphorylate the tyrosine residues in the CTD. Interestingly, the Drosophila or the yea st CTD were not efficiently phosphorylated by the mammalian c-Abl. This spe cies-specificity was found to be determined by the extreme COOH-terminal CT D sequences that are not conserved through evolution. In vitro, COOH-termin al-truncated CTD could neither bind to, nor be phosphorylated by, c-Abl. In vivo, coexpression of a full length CTD prevents c-Abl from inducing the t yrosine phosphorylation of endogenous RNA polymerase II, and such inhibitor y effect was not observed with the coexpression of COOH-terminal-truncated CTD, Serine/threonine phosphorylation of the CTD has been linked to the reg ulation of transcription elongation. Transcription from the human immunodef iciency virus type 1 (HIV-1) promoter requires CTD-phosphorylation, which i s stimulated by the viral Tat protein through the recruitment of cellular S er/Thr CTD kinases. In transient cotransfection experiments, the c-Abl kina se was found to activate the HIV promoter in the absence of Tat, The activa tion of the HIV promoter required the nuclear localization of c-Abl and cou ld be correlated with increased tyrosine phosphorylation of RNA polymerase II. These observations suggest that tyrosine phosphorylation of the CTD may be functionally equivalent to its serine/threonine phosphorylation in stim ulating transcription elongation.