Repression Of Matrix Gene Expression By B-Myb

Abstract

Vascular smooth muscle cells (SMCs) synthesise collagens type I and V matrix proteins, which are major constituents of the arterial wall. In culture, matrix gene expression varies inversely with the rate of SMC proliferation. Previously we showed that B-myb, a member of the myb gene family, is expressed in SMCs in a cell-cycle dependent fashion, and that it is a negative regulator of matrix gene transcription. Phosphorylation by cyclin A/cdk2 relieved B-Myb-mediated repression of α2 (V) collagen gene transcription, and the sites of phosphorylation were distinct from those affecting activation by B-Myb. The domain responsible for repression mapped to residues 491 to 582 of the C-terminal region of B-Myb. Transgenic mice over-expressing B- Myb displayed significantly reduced collagen expression in the aorta. Thus, B-Myb functions in vivo as a repressor of collagen gene expression in vascular SMCs.