Interaction between cyclin T1 and SCFSKP2 targets CDK9 for ubiquitination and degradation by the proteasome

被引:83
作者
Kiernan, RE
Emiliani, S
Nakayama, E
Castro, A
Labbé, JC
Lorca, T
Nakayama, K
Benkirane, A
机构
[1] Ctr Rech Biochim Macromol, UPR 1086, Montpellier, France
[2] Kyushu Univ, Lab Embryon & Genet Engn, Fukuoka 812, Japan
[3] Kyushu Univ, Dept Mol & Cellular Biol, Med Inst Bioregulat, Fukuoka 812, Japan
关键词
D O I
10.1128/MCB.21.23.7956-7970.2001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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 SCFSKP2 is mediated by cyclin T1 while ubiquitination occurs exclusively on CDK9.
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收藏
页码:7956 / 7970
页数:15
相关论文
共 52 条
  • [1] SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box
    Bai, C
    Sen, P
    Hofmann, K
    Ma, L
    Goebl, M
    Harper, JW
    Elledge, SJ
    [J]. CELL, 1996, 86 (02) : 263 - 274
  • [2] Activation of integrated provirus requires histone acetyltransferase - p300 AND P/CAF are coactivators for HIV-1 Tat
    Benkirane, M
    Chun, RF
    Xiao, H
    Ogryzko, VV
    Howard, BH
    Nakatani, Y
    Jeang, KT
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (38) : 24898 - 24905
  • [3] Recruitment of cyclin T1/P-TEFb to an HIV type I long terminal repeat promoter proximal RNA target is both necessary and sufficient for full activation of transcription
    Bieniasz, PD
    Grdina, TA
    Bogerd, HP
    Cullen, BR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (14) : 7791 - 7796
  • [4] SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
    Carrano, AC
    Eytan, E
    Hershko, A
    Pagano, M
    [J]. NATURE CELL BIOLOGY, 1999, 1 (04) : 193 - 199
  • [5] The ubiquitin-proteasome pathway: on protein death and cell life
    Ciechanover, A
    [J]. EMBO JOURNAL, 1998, 17 (24) : 7151 - 7160
  • [6] Cooper KF, 1999, GENE EXPRESSION, V8, P43
  • [7] ELLISON MJ, 1991, J BIOL CHEM, V266, P21150
  • [8] Antiapoptotic function of Cdk9 (TAK/P-TEFb) in U937 promonocytic cells
    Foskett, SM
    Ghose, R
    Tang, DN
    Lewis, DE
    Rice, AP
    [J]. JOURNAL OF VIROLOGY, 2001, 75 (03) : 1220 - 1228
  • [9] Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription
    Fu, TJ
    Peng, JM
    Lee, G
    Price, DH
    Flores, O
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (49) : 34527 - 34530
  • [10] The interaction between HIV-1 Tat and human cyclin T1 requires zinc and a critical cysteine residue that is not conserved in the murine CycT1 protein
    Garber, ME
    Wei, P
    KewalRamani, VN
    Mayall, TP
    Herrmann, CH
    Rice, AP
    Littman, DR
    Jones, KA
    [J]. GENES & DEVELOPMENT, 1998, 12 (22) : 3512 - 3527