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Molecular and Cellular Biology, December 2001, p. 7956-7970, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.7956-7970.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Interaction between Cyclin T1 and SCFSKP2 Targets CDK9 for Ubiquitination and Degradation by the Proteasome

Rosemary E. Kiernan,1,* Stéphane Emiliani,1 Keiko Nakayama,2 Anna Castro,3 Jean Claude Labbé,3 Thierry Lorca,3 Kei-ichi Nakayama,2,4 and Monsef Benkirane1

Laboratoire de Virologie Moléculaire et Transfert de Gène, Institut de Génétique Humaine, UPR1142,1 and Centre de Recherche Biochimie Macromoléculaire, UPR1086,3 Montpellier, France, and Laboratory of Embryonic and Genetic Engineering2 and Department of Molecular and Cellular Biology,4 Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

Received 21 May 2001/Returned for modification 19 July 2001/Accepted 28 August 2001

CDK9 paired with cyclin T1 forms the human P-TEFb complex and stimulates productive transcription through phosphorylation of the RNA polymerase II C-terminal domain. Here we report that CDK9 is ubiquitinated and degraded by the proteasome whereas cyclin T1 is stable. SCFSKP2 was recruited to CDK9/cyclin T1 via cyclin T1 in an interaction requiring its PEST domain. CDK9 ubiquitination was modulated by cyclin T1 and p45SKP2. CDK9 accumulated in p45SKP2-/- cells, and its expression during the cell cycle was periodic. The transcriptional activity of CDK9/cyclin T1 on the class II major histocompatibility complex promoter could be regulated by CDK9 degradation in vivo. We propose a novel mechanism whereby recruitment of SCFSKP2 is mediated by cyclin T1 while ubiquitination occurs exclusively on CDK9.

* Corresponding author. Mailing address: Laboratoire de Virologie Moléculaire et Transfert de Gène, Institut de Génétique Humaine, UPR1142, 141 rue de la Cardonille, Montpellier, 34396, France. Phone: 33 4 99 61 99 32. Fax: 33 4 99 61 99 01. E-mail: rkiernan{at}igh.cnrs.fr.

Molecular and Cellular Biology, December 2001, p. 7956-7970, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.7956-7970.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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