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Transcriptional regulation by protein kinase CDC2L5

$48,296F32FY2005AINIH

University Of California Berkeley, Berkeley CA

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Abstract

DESCRIPTION (provided by applicant): The CDC2-related protein kinase, CDC2L5, shares extensive sequence homology and characteristics with CDK9, the kinase subunit of the general transcription elongation factor P-TEFb, which is also important for the replication of HIV in its host. This study will try to determine the functions of CDC2L5, in relation to CDK9's ability to activate general and HIV transcription. The kinase and transcription activities of CDC2L5 will be characterized and compared to those of CDK9. Moreover, since an RS domain common to all splicing factors is also found in CDC2L5, splicing assay will be performed to examine the possible involvement of CDC2L5 in HIV mRNA splicing. Finally, the expression of endogenous CDC2L5 will be suppressed by RNA interfering technique, followed by gene expression analysis with DNA microarray technology to determine the affected genes and thus the unique physiological function of CDC2L5. The information gains from this study could be useful for developing new methods for AIDS therapy by specifically targeting these cellular events governed by CDC2L5.

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