Cyclin A–CDK phosphorylates Sp1 and enhances Sp1-mediated transcription

Patrick Fojas de Borja; N.Keith Collins; Ping Du; Jane Azizkhan-Clifford; Maria Mudryj

doi:10.1093/emboj/20.20.5737

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Cyclin A–CDK phosphorylates Sp1 and enhances Sp1-mediated transcription

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Cyclin A–CDK phosphorylates Sp1 and enhances Sp1-mediated transcription

Patrick Fojas de Borja, N.Keith Collins, Ping Du, Jane Azizkhan-Clifford and Maria Mudryj

The EMBO journal, v 20(20), pp 5737-5747

15 Oct 2001

DOI: https://doi.org/10.1093/emboj/20.20.5737

PMID: 11598016

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Abstract

transcription

cyclin A

cyclin-dependent kinase

Sp1

Cyclin A-mediated activation of cyclin-dependent kinases (CDKs) is essential for cell cycle transversal. Cyclin A activity is regulated on several levels and cyclin A elevation in a number of cancers suggests a role in tumorigenesis. In the present study, we used a modified DNA binding site selection and PCR amplification procedure to identify DNA binding proteins that are potential substrates of cyclin A–CDK. One of the sequences identified is the Sp1 transcription factor binding site. Co-immunoprecipitation experiments show that cyclin A and Sp1 can interact physically. In vitro and in vivo phosphorylation studies indicate that cyclin A–CDK complexes can phosphorylate Sp1. The phosphorylation site is located in the N-terminal region of the protein. Cells overexpressing cyclin A have elevated levels of Sp1 DNA binding activity, suggesting that cyclin A–CDK-mediated phosphorylation augments Sp1 DNA binding properties. In co-transfection studies, cyclin A expression stimulated transcription from an Sp1-regulated promoter. Mutation of the phosphorylation site abrogated cyclin A–CDK-dependent phosphorylation, augmentation of Sp1 transactivation function and DNA binding activity.

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Title: Cyclin A–CDK phosphorylates Sp1 and enhances Sp1-mediated transcription
Creators: Patrick Fojas de Borja - Department of Medical Microbiology and Immunology, University of California, Davis, CA 95616 and Martinez Veterans Affairs, Martinez, CA 94553
N.Keith Collins - Department of Medical Microbiology and Immunology, University of California, Davis, CA 95616 and Martinez Veterans Affairs, Martinez, CA 94553
Ping Du - Department of Medical Microbiology and Immunology, University of California, Davis, CA 95616 and Martinez Veterans Affairs, Martinez, CA 94553
Jane Azizkhan-Clifford - Department of Medical Microbiology and Immunology, University of California, Davis, CA 95616 and Martinez Veterans Affairs, Martinez, CA 94553
Maria Mudryj - Department of Medical Microbiology and Immunology, University of California, Davis, CA 95616 and Martinez Veterans Affairs, Martinez, CA 94553
Publication Details: The EMBO journal, v 20(20), pp 5737-5747
Publisher: Oxford University Press; Oxford, UK
Resource Type: Journal article
Language: English
Academic Unit: Biochemistry and Molecular Biology
Web of Science ID: WOS:000171766300019
Scopus ID: 2-s2.0-0035887030
Other Identifier: 991014878262604721

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Collaboration types: Domestic collaboration
Web of Science research areas: Biochemistry & Molecular Biology; Cell Biology