Nuclear c-Abl is a COOH-terminal repeated domain (CTD)-tyrosine (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 yeast CTD were not efficiently phosphorylated by the mammalian c-Abl. This species-specificity was found to be determined by the extreme COOH-terminal CTD sequences that are not conserved through evolution. In vitro, COOH-terminal-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 tyrosine phosphorylation of endogenous RNA polymerase II, and such inhibitory effect was not observed with the coexpression of COOH-terminal-truncated CTD. Serine/threonine phosphorylation of the CTD has been linked to the regulation of transcription elongation. Transcription from the human immunodeficiency virus type 1 (HIV-1) promoter requires CTD-phosphorylation, which is stimulated by the viral Tat protein through the recruitment of cellular Ser/Thr CTD kinases. In transient cotransfection experiments, the c-Abl kinase was found to activate the HIV promoter in the absence of Tat. The activation of the HIV promoter required the nuclear localization of c-Abl and could 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 stimulating transcription elongation.
Department of Biology, Center for Molecular Genetics, University of California, San Diego, La Jolla 92093-0322, USA.
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Baskaran
S R
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Escobar
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JY
Wang
D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology; D015967:Gene Expression Regulation, Viral; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000235:genetics; D006801:Humans; D008322:Mammals; D051379:Mice; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism / Q000502:physiology*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism; D015003:Yeasts / Q000201:enzymology
D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D005982:Glutathione Transferase; D016315:Proto-Oncogene Proteins c-abl; D012319:RNA Polymerase II