Transcriptional activity and substrate recognition of cyclin T2 from P-TEFb.
Transcriptional elongation by RNA polymerase II (RNAPII) is regulated by the positive transcription elongation factor b (P-TEFb), which contains Cdk9 and a C-type cyclin (CycT1, CycT2a, CycT2b, or CycK). Whereas their N-terminal cylin boxes are almost identical, the C-terminal sequences of CycT1 and CycT2 are divergent. Previously, a histidine-rich stretch in CycT1 was found to bind the CTD of RNAPII and direct the transcriptional activity of this P-TEFb complex when tethered artificially to DNA. The global repressor PIE-1 from C. elegans blocked its effects. In this study, C-terminal truncations of CycT2 past its histidine-rich stretch, to a leucine-rich region next to its cyclin boxes, still maintained appreciable transcriptional activity. Moreover, this domain bound RNAPII via its CTD and PIE-1 blocked its effects. Thus, CycT2 not only contains two domains that target RNAPII but this substrate recognition is necessary for its transcriptional activity via DNA.
Kurosu
Takeshi
T
Department of Medicine, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA 94143-0703, USA.
Zhang
Fan
F
Peterlin
B Matija
BM
D045744:Cell Line, Tumor; D056906:Cyclin T; D016213:Cyclins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D016296:Mutagenesis; D010957:Plasmids; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection
C503684:CCNT1 protein, human; C441622:CCNT2 protein, human; D056906:Cyclin T; D016213:Cyclins; D004273:DNA, Neoplasm; D012097:Repressor Proteins; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II