B-MYB EXPRESSION IN VASCULAR SMOOTH-MUSCLE CELLS OCCURS IN A CELL CYCLE-DEPENDENT FASHION AND DOWN-REGULATES PROMOTER ACTIVITY OF TYPE-I COLLAGEN GENES
Dj. Marhamati et Ge. Sonenshein, B-MYB EXPRESSION IN VASCULAR SMOOTH-MUSCLE CELLS OCCURS IN A CELL CYCLE-DEPENDENT FASHION AND DOWN-REGULATES PROMOTER ACTIVITY OF TYPE-I COLLAGEN GENES, The Journal of biological chemistry, 271(7), 1996, pp. 3359-3365
The members of the Myb family of transcription factors are defined by
homology in the DNA-binding domain; all bind the Myb-binding site (MBS
) sequence (YG(A/G)C(A/C/G)GTT(G/A)). Here we report that cultured bov
ine vascular smooth muscle cells (SMCs) express B-myb. Levels of B-myb
RNA found in exponential growth were reduced dramatically in serum-de
prived quiescent SMCs; B-myb mRNA levels increased in the cell cycle d
uring the late G(1) to S phase transition following restimulation with
serum, epidermal growth factor, or phorbol ester plus insulin-like gr
owth factor-1. Changes in the rate of B-myb gene transcription could a
ccount for part of the observed increase following serum addition. Tre
atment of SMC cultures with actinomycin D indicated a >4-h half-life f
or B-myb mRNA during the S phase of the cell cycle. Cotransfection of
either a bovine or human B-myb expression vector down-regulated the ac
tivity of a multimerized MBS element-driven reporter construct in SMCs
. Putative MBS elements were detected upstream of the promoters of the
two chains of type I collagen, which we have found to be expressed in
versely with growth state of the SMC (Kindy, M. S., Chang, C.-J., and
Sonenshein, G. E. (1988) J. Biol. Chem. 263, 11426-11430). In cotransf
ection experiments, B-myb expression down-regulated the promoter activ
ity of alpha 1(I) and alpha 2(I) collagen constructs an average of 92
and 82%, respectively. Thus, B-myb represents a potential link in the
observed inverse relationship between collagen gene expression and gro
wth of vascular SMCs.