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Cited by 519

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Identification of multiple cyclin subunits of human P-TEFb

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Peng, J., Zhu, Y., Milton, J. T., Price, D. H.·1998·Genes & Development

Abstract

The transition from abortive into productive elongation is proposed to be controlled by a positive transcription elongation factor b (P-TEFb) through phosphorylation of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II. Drosophila P-TEFb was identified recently as a cyclin-dependent kinase (CDK9) paired with a cyclin subunit (cyclin T). We demonstrate here the cloning of multiple cyclin subunits of human P-TEFb (T1 and T2). Cyclin T2 has two forms (T2a and T2b) because of alternative splicing. Both cyclin T1 and T2 are ubiquitously expressed. Immunoprecipitation and immunodepletion experiments carried out on HeLa nuclear extract (HNE) indicated that cyclin T1 and T2 were associated with CDK9 in a mutually exclusive manner and that almost all CDK9 was associated with either cyclin T1 or T2. Recombinant CDK9/cyclin T1, CDK9/cyclin T2a, and CDK9/cyclin T2b produced in Sf9 cells possessed DRB-sensitive kinase activity and functioned in transcription elongation in vitro. Either cyclin T1 or T2 was required to activate CDK9, and the truncation of the carboxyl terminus of the cyclin reduced, but did not eliminate, P-TEFb activity. Cotransfection experiments indicated that all three CDK9/cyclin combinations dramatically activated the CMV promoter.

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Metadata

Authors
Peng, J., Zhu, Y., Milton, J. T., & Price, D. H.
Venue
Genes & Development
Published
1998-03-01
Volume
12
Issue
5
Pages
755-762
ISSN
0890-9369 (ISSN-L)
OpenAlex
W1973000551
Cited by
519
References
2
Type
posted content
Language
en
Open access
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CoChat. (2026). Citation check: Identification of multiple cyclin subunits of human P-TEFb. https://app.cochat.ai/papers/10.1101/gad.12.5.755
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Peng, J., Zhu, Y., Milton, J. T., & Price, D. H. (1998). Identification of multiple cyclin subunits of human P-TEFb. Genes & Development. https://doi.org/10.1101/gad.12.5.755

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