Interaction between cyclin T1 and SCF(SKP2) targets CDK9 for ubiquitination and degradation by the proteasome.
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.
Kiernan
R E
RE
Laboratoire de Virologie Moléculaire et Transfert de Gène, Institut de Génétique Humaine, UPR1142, Montpellier, France. rkiernan@igh.cnrs.fr
Emiliani
S
S
Nakayama
K
K
Castro
A
A
Labbé
J C
JC
Lorca
T
T
Nakayama Ki
K
K
Benkirane
M
M
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D056906:Cyclin T; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D010507:Periodicity; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
C503684:CCNT1 protein, human; C503685:Ccnt1 protein, mouse; D018797:Cell Cycle Proteins; D056906:Cyclin T; D016213:Cyclins; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; D044786:S-Phase Kinase-Associated Proteins; D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; C467969:CDK9 protein, human; C467972:Cdk9 protein, mouse; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases