Modulation of Sp1 activity by a cyclin A/CDK complex.
Transcription factors of the Sp1 family are targets of several regulatory pathways and can induce or inhibit gene expression. Here we show that Sp1 is associated with a histone 1 kinase activity. This activity is growth regulated and correlates with the expression of cyclin A. Co-immunoprecipitation experiments demonstrate, that Sp1 interacts with cyclin A and can be phosphorylated by a cyclin A associated kinase. The interaction is direct and requires the zinc-finger region of Sp1 and the amino-terminal domain of cyclin A. Over-expression of cyclin A enhances the expression of a reporter gene controlled by an Sp1 responsive promoter. Addition of olomoucine, a specific inhibitor of CDK2 and CDC2 activity on the other hand reduces the expression of the reporter. Electrophoretic mobility shift assays suggest that this is due to a reduction of the DNA-binding ability of Sp1 family members. Our results indicate that phosphorylation of Sp1 and other members of the family by a cyclin A/CDK complex may play a role in the growth and cell cycle regulation of its transcriptional activity.
Institute of Medical Biochemistry, Division of Molecular Biology, Vienna Biocenter, University of Vienna, Vienna, A-1030, Austria.
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Haidweger
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Novy
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Rotheneder
D000818:Animals; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D002460:Cell Line; D019925:Cyclin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D007701:Kinetin; D010766:Phosphorylation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017434:Protein Structure, Tertiary; D011687:Purines / Q000494:pharmacology; D020218:Response Elements / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism; D016335:Zinc Fingers
D019925:Cyclin A; D004268:DNA-Binding Proteins; D006657:Histones; D011687:Purines; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; C090046:olomoucine; D004247:DNA; D011494:Protein Kinases; C102333:histone H1 kinase; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D007701:Kinetin