Ka. Comer et al., HUMAN SMOOTH-MUSCLE ALPHA-ACTIN GENE IS A TRANSCRIPTIONAL TARGET OF THE P53 TUMOR-SUPPRESSOR PROTEIN, Oncogene, 16(10), 1998, pp. 1299-1308
Smooth muscle (sm) alpha-actin is expressed in vascular smooth muscle
cells and fibroblast cells. Its expression is regulated by cell prolif
eration and repressed during oncogenic transformation, In this study,
we demonstrate that p53 activation is associated with a dramatic incre
ase in organized microfilament bundles and an increase in sm alpha-act
in mRNA level. Wild-type p53, but not mutant p53, strongly stimulated
human sm alpha-actin promoter activity in p53 null cell lines. The seq
uences homologous to the p53 consensus sequence and to the p53 binding
sequence from the muscle creatine kinase, were found within a specifi
c region of the sm alpha-actin promoter. This sequence was sufficient
to confer p53-dependent activation to a heterologous promoter and p53
was capable of binding to this sequence as assessed by gel shift analy
sis. Ionizing irradiation of colorectal tumor cells caused an increase
in alpha-actin mRNA level in a p53-dependent manner. Taken together,
these results demonstrate that human sm alpha-actin gene is a transcri
ptional target for p53 tumor suppressor protein and represents the fir
st example of a cytoskeletal gene with a functionally defined p53 resp
onse element.