33 Structure and Function of Serum Response Factor

Abstract

OVERVIEW
Serum response factor (SRF) is a transcription factor that binds to a common regulatory element found in the promoters of many genes that are transiently activated by growth factor stimulation. In this chapter, I summarize our current knowledge of SRF as a member of a novel class of DNA-binding proteins and review current findings concerning its regulation and interactions with other proteins. Following a discussion of the function of the Saccharomyces cerevisiae MCM1 protein, which provides useful ideas concerning the possible molecular mechanisms of SRF function, the role of SRF in the function of the SRE is discussed.

INTRODUCTION
Stimulation of cells by growth factors or mitogens transiently activates transcription of a large family of genes, including the proto-oncogenes c-fos, c-jun, c-myc, and c-rel, without the need for prior protein synthesis. Many of these genes encode transcriptional regulatory proteins, the expression of which is presumed to determine the subsequent response of the genome, and ultimately of the cell, to growth factor stimulation (see Almendral et al. 1988; Bravo 1990). In many cases, transcriptional activation occurs immediately upon stimulation, reaches a peak within 15–30 minutes, and ceases after an hour. By analogy with the cascade of viral gene expression that occurs during lytic infection by DNA viruses, these genes have been termed cellular “immediate-early” genes.

A common cis-regulatory element, the serum response element (SRE; Treisman 1985, 1986; Gilman et al. 1986; Greenberg et al. 1987), has been identified that is in large part responsible for transcriptional regulation of the...