Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics Journal Article

  


Authors: Larochelle, S.; Batliner, J.; Gamble, M. J.; Barboza, N. M.; Kraybill, B. C.; Blethrow, J. D.; Shokat, K. M.; Fisher, R. P.
Article Title: Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics
Abstract: Cdk7 performs two essential but distinct functions as a CDK-activating kinase (CAK) required for cell-cycle progression and as the RNA polymerase II (Pol II) CTD kinase of general transcription factor IIH. To investigate the substrate specificity underlying this dual function, we created an analog-sensitive (AS) Cdk7 able to use bulky ATP derivatives. Cdk7-AS-cyclin H-Mat1 phosphorylates ∼10-15 endogenous polypeptides in nuclear extracts. We identify seven of these as known and previously unknown Cdk7 substrates that define two classes: proteins such as Pol II and transcription elongation factor Spt5, recognized efficiently only by the fully activated Cdk7 complex, through sequences surrounding the site of phosphorylation; and CDKs, targeted equivalently by all active forms of Cdk7, dependent on substrate motifs remote from the phosphoacceptor residue. Thus, Cdk7 accomplishes dual functions in cell-cycle control and transcription not through promiscuity but through distinct, stringent modes of substrate recognition. © 2006 Nature Publishing Group.
Keywords: controlled study; unclassified drug; human cell; protein function; protein motif; cell cycle; complex formation; protein binding; transcription factor; enzyme activation; enzyme activity; peptide; enzyme substrate; hela cells; phosphorylation; enzyme phosphorylation; transcription regulation; amino acid sequence; conserved sequence; molecular sequence data; sequence alignment; molecular recognition; substrate specificity; chemical genetics; cell nucleus; adenosine triphosphate; sequence homology; enzyme specificity; cyclin-dependent kinases; cell cycle regulation; enzyme subunit; rna polymerase ii; cell extracts; enzyme active site; cyclin dependent kinase 7; cyclin dependent kinase activating kinase; protein spt5; functional proteomics; transcription elongation factor; adenosine triphosphate derivative
Journal Title: Nature Structural and Molecular Biology
Volume: 13
Issue: 1
ISSN: 1545-9993
Publisher: Nature Publishing Group  
Date Published: 2006-01-01
Start Page: 55
End Page: 62
Language: English
DOI: 10.1038/nsmb1028
PUBMED: 16327805
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-30044438459&partnerID=40&md5=105df4df816cb8e33a0331e6f905b995
Notes: --- - "Cited By (since 1996): 30" - "Export Date: 4 June 2012" - "CODEN: NSMBC" - "Source: Scopus"
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MSK Authors
  1. Nora M Barboza
    2 Barboza
  2. Matthew J Gamble
    7 Gamble
  3. Robert P Fisher
    28 Fisher
  4. Stephane Larochelle
    10 Larochelle
  5. Jasmin Batliner
    1 Batliner
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