Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome

• Published in: Molecular and cellular biology 2001-12, Vol.21 (23), p.7956-7970
• Main Authors: Kiernan, R E, Emiliani, S, Nakayama, K, Castro, A, Labbé, J C, Lorca, T, Nakayama Ki, K, Benkirane, M
• Format: Article
• Language: English
• Subjects: Anaphase-Promoting Complex-Cyclosome; Animals; Cell Cycle - physiology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cells, Cultured; Cyclin T; Cyclin-Dependent Kinase 9; Cyclin-Dependent Kinases - metabolism; Cyclins - metabolism; Cysteine Endopeptidases - metabolism; Fibroblasts - metabolism; Humans; Ligases - metabolism; Mice; Multienzyme Complexes - metabolism; Periodicity; Proteasome Endopeptidase Complex; Protein Binding - physiology; Protein Structure, Tertiary - physiology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; S-Phase Kinase-Associated Proteins; Transcription, Genetic - physiology; Transfection; Ubiquitin-Protein Ligase Complexes; Ubiquitin-Protein Ligases; Ubiquitins - metabolism
• ISSN: 0270-7306
• DOI: 10.1128/MCB.21.23.7956-7970.2001

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. SCF(SKP2) was recruited to CDK9/cyclin T1 via cyclin T1 in an interaction requiring its PEST domain. CDK9 ubiquitination was modulated by cyclin T1 and p45(SKP2). CDK9 accumulated in p45(SKP2-/-) 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 SCF(SKP2) is mediated by cyclin T1 while ubiquitination occurs exclusively on CDK9.