title: PITSLRE p110 protein kinases associate with transcription complexes and affect their activity.
abstract: Although the PITSLRE protein kinases are members of the cyclin-dependent kinase superfamily, their cellular function is unclear. Previously we demonstrated that the general RNA splicing factor RNPS1 is a specific PITSLRE p110 kinase interactor in vivo. This suggests that the PITSLRE family of protein kinases is involved in some aspect of RNA processing or transcription. Here we identify multiple transcriptional elongation factors, including ELL2, TFIIF(1), TFIIS, and FACT, as PITSLRE kinase-associated proteins. We demonstrate that PITSLRE p110 protein kinases co-immunoprecipitate and/or co-purify with these elongation factors as well as with RNA polymerase II. Antibody-mediated inhibition of PITSLRE kinase specifically suppressed RNA polymerase II-dependent in vitro transcription initiated at a GC-rich (adenosine deaminase) or TATA box-dependent (Ad2ML) promoter, and this suppression was rescued by readdition of purified PITSLRE p110 kinase. Together, these data strongly suggest that PITSLRE protein kinases participate in a signaling pathway that potentially regulates or links transcription and RNA processing events.
authors.affiliation: Department of Tumor Cell Biology and the Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Janeen H
authors.initials: JH
authors.lastname: Trembley
authors.forename: Dongli
authors.initials: D
authors.lastname: Hu
authors.forename: Li-Chung
authors.initials: LC
authors.lastname: Hsu
authors.forename: Cho-Yau
authors.initials: CY
authors.lastname: Yeung
authors.forename: Clive
authors.initials: C
authors.lastname: Slaughter
authors.forename: Jill M
authors.initials: JM
authors.lastname: Lahti
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Kidd
mesh_terms: D000818:Animals; D018844:Cyclin-Dependent Kinases; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D005656:Fungal Proteins / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006609:High Mobility Group Proteins; D006801:Humans; D019169:Jurkat Cells; D013058:Mass Spectrometry; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry*; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012318:RNA Polymerase I / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism; D035165:Transcription Factors, General; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; C447613:ELL2 protein, human; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D006609:High Mobility Group Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; C073537:SSRP1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D035165:Transcription Factors, General; D019473:Transcription Factors, TFII; D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; D012313:RNA; D005982:Glutathione Transferase; D010770:Phosphotransferases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases; D012318:RNA Polymerase I; C056604:transcription factor TFIIF