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M110771200v1
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Papers In Press, published online ahead of print November 27, 2001
J. Biol. Chem, 10.1074/jbc.M110771200
Submitted on November 9, 2001
Revised on November 27, 2001
Accepted on November 27, 2001

GC-box binding transcription factors control the neuronal specific expression of the cdk5 regulator p35

Sarah Ross, Anri Tienhaara, Ming-Sum Lee, Li-Huei Tsai, and Grace Gill

Department of of Pathology, Harvard Medical School, Boston, MA 02115

Corresponding Author: grace_gill{at}hms.harvard.edu

Cdk5/p35 kinase activity is highest in post-mitotic neurons of the central nervous system and is critical for development and function of the brain. The neuronal specific activity of the cdk5/p35 kinase is achieved through the regulated expression of p35 mRNA. We have identified a small 200bp fragment of the p35 promoter that is sufficient for high levels of neuronal specific expression. Mutational analysis of this TATA-less promoter has identified a 17bp GC-rich element, present twice, that is both required for promoter activity and sufficient for neuronal specific transcription. A GC-box within the 17bp element is critical for both promoter activity and protein-DNA complex formation. The related transcription factors Sp1, Sp3 and Sp4 constitute most of the GC-box DNA-binding activity in neurons. We have found that both the relative contribution of the Sp family proteins to GC-box binding and the transcriptional activity of these proteins is regulated during neuronal differentiation. Thus, our data shows that the GCbox binding Sp proteins contribute to the regulation of p35 expression in neurons, suggesting changes in the Sp transcription factors level and activity may contribute to cell type specific expression of many genes in the central nervous system.


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