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Initial characterization of the Rho B promoter

University of British Columbia

Quiescent cells can be stimulated to proliferate or differentiate by extracellular signals which initiate cascades of tyrosine and serine/threonine kinases. Signaling pathways terminate in the nucleus where they can cause activation or suppression of gene expression. Immediate early genes are the initial genes induced at the level of transcription by mitogenic signals. The transcriptional induction of these genes occurs very rapidly after mitogenic stimulation and does not depend on de novo protein synthesis. This enhancement of transcription is transient producing mRNA species which are labile. In order to understand the signaling processes which lead to cellular proliferation, it is crucial to understand the mechanisms which control transcriptional induction of immediate early genes. Pathways which lead to the final event of transcription can be delineated by identifying and characterizing the factors which directly associate with the promoters of these genes and result in transcriptional induction. Rho B (ras homologous B) is the first and only member of the ras family of GTPases which has been classified as an immediate early gene. Evidence suggests that transcriptional regulation of Rho B is unique in comparison with other immediate early genes; therefore, studying its transcriptional induction should lead to a better understanding of signaling pathways which trigger the proliferative cycle of the cell. Here I show Rho B is an intronless gene with a TATA-less promoter containing a consensus initiator core element, -3' CGCAGTCC+5'. Rho B transcription initiates at multiple closely spaced nucleotides, CGCA, with the A nucleotide representing the major start site. I describe possible functions for putative protein binding sites in the 1 kb 5'-flanking region and propose that the czs-elements responsible for mitogenic stimulation of Rho B transcription are not located within the 3.2 kb 5'-flanking region relative to the start site.

Thesis/Dissertation

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2009-02-14

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http://hdl.handle.net/2429/4584

Biochemistry and Molecular Biology

University of British Columbia

UBCV

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