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Article: Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated Tat stimulation of HIV-1 transcription

TitleRequirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated Tat stimulation of HIV-1 transcription
Authors
Issue Date2000
Citation
Journal of Biological Chemistry, 2000, v. 275, n. 1, p. 279-287 How to Cite?
AbstractTat activation of HIV-1 transcription is mediated by human transcription elongation factor P-TEFb, which interacts with Tat and phosphorylates the C- terminal domain of RNA polymerase II. The catalytic subunit of the P-TEFb complex, Cdk9, has been shown to interact with cyclin T and several other proteins of unknown identity. Consequently, the exact subunit composition of active P-TEFb has not been determined. Here we report the affinity purification and identification of the Cdk9-associated proteins. In addition to forming a heterodimer with cyclin T1, Cdk9 interacted with the molecular chaperone Hsp70 or a kinase-specific chaperone complex, Hsp90/Cdc37, to form two separate chaperone-Cdk9 complexes. Although the Cdk9/cyclin T1 dimer was exceptionally stable and produced slowly in the cell, free and unprotected Cdk9 appeared to be degraded rapidly. Several lines of evidence indicate the heterodimer of Cdk9/cyclin T1 to be the mature, active form of P-TEFb responsible for phosphorylation of the C-terminal domain of RNA polymerase II interaction with the Tat activation domain, and mediation of Tat activation of HIV-1 transcription. Pharmacological inactivation of Hsp90/Cdc37 function by geldanamycin revealed an essential role for the chaperone-Cdk9 complexes in generation of Cdk9/cyclin T1. Our data suggest a previously unrecognized chaperone-dependent pathway involving the sequential actions of Hsp70 and Hsp90/Cdc37 in the stabilization/folding of Cdk9 as well as the assembly of an active Cdk9/cyclin T1 complex responsible for P-TEFb-mediated Tat transactivation.
Persistent Identifierhttp://hdl.handle.net/10722/323762
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorO'Keeffe, Bridget-
dc.contributor.authorFong, Yick-
dc.contributor.authorChen, Dan-
dc.contributor.authorZhou, Sharleen-
dc.contributor.authorZhou, Qiang-
dc.date.accessioned2023-01-13T02:59:10Z-
dc.date.available2023-01-13T02:59:10Z-
dc.date.issued2000-
dc.identifier.citationJournal of Biological Chemistry, 2000, v. 275, n. 1, p. 279-287-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/323762-
dc.description.abstractTat activation of HIV-1 transcription is mediated by human transcription elongation factor P-TEFb, which interacts with Tat and phosphorylates the C- terminal domain of RNA polymerase II. The catalytic subunit of the P-TEFb complex, Cdk9, has been shown to interact with cyclin T and several other proteins of unknown identity. Consequently, the exact subunit composition of active P-TEFb has not been determined. Here we report the affinity purification and identification of the Cdk9-associated proteins. In addition to forming a heterodimer with cyclin T1, Cdk9 interacted with the molecular chaperone Hsp70 or a kinase-specific chaperone complex, Hsp90/Cdc37, to form two separate chaperone-Cdk9 complexes. Although the Cdk9/cyclin T1 dimer was exceptionally stable and produced slowly in the cell, free and unprotected Cdk9 appeared to be degraded rapidly. Several lines of evidence indicate the heterodimer of Cdk9/cyclin T1 to be the mature, active form of P-TEFb responsible for phosphorylation of the C-terminal domain of RNA polymerase II interaction with the Tat activation domain, and mediation of Tat activation of HIV-1 transcription. Pharmacological inactivation of Hsp90/Cdc37 function by geldanamycin revealed an essential role for the chaperone-Cdk9 complexes in generation of Cdk9/cyclin T1. Our data suggest a previously unrecognized chaperone-dependent pathway involving the sequential actions of Hsp70 and Hsp90/Cdc37 in the stabilization/folding of Cdk9 as well as the assembly of an active Cdk9/cyclin T1 complex responsible for P-TEFb-mediated Tat transactivation.-
dc.languageeng-
dc.relation.ispartofJournal of Biological Chemistry-
dc.titleRequirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated Tat stimulation of HIV-1 transcription-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.275.1.279-
dc.identifier.pmid10617616-
dc.identifier.scopuseid_2-s2.0-0034614455-
dc.identifier.volume275-
dc.identifier.issue1-
dc.identifier.spage279-
dc.identifier.epage287-
dc.identifier.isiWOS:000085951600040-

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