Recombinant adenovirus expressing Von Hippel-Lindau-mediated cell cycle arrest is associated with the induction of cyclin-dependent kinase inhibitor p27(Kip1)
M. Kim et al., Recombinant adenovirus expressing Von Hippel-Lindau-mediated cell cycle arrest is associated with the induction of cyclin-dependent kinase inhibitor p27(Kip1), BIOC BIOP R, 253(3), 1998, pp. 672-677
Citations number
20
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
A recombinant adenovirus containing the Von Hippel-Lindau (VHL) cDNA was co
nstructed (AdVHL) and used to investigate the function of this tumor suppre
ssor gene. Exposure of renal and breast cancer cell lines to AdVHL resulted
in high levels of VHL mRNA and protein. AdVHL infection resulted in G1 cel
l cycle arrest and growth inhibition of renal and breast cancer cell lines.
AdVHL-mediated cell cycle arrest was associated with induction of the cycl
in-dependent kinase inhibitor (CDKI) p27(Kip1) and inhibition of CDK2 and c
yclinB1-dependent cdc2 activities. Nuclear run-on analyses and actinomycin
D inhibition studies indicate that the induction of p27(Kip1) RNA by VHL is
mediated at least in part through an increase in p27(Kip1) mRNA synthesis.
Furthermore, [S-35]methionine pulse-chase studies indicate that the increa
se in p27(Kip) expression is also regulated through posttranscriptional con
trol mechanisms. These studies support a novel concept that the tumor suppr
essor gene VHL controls cell cycle progression by regulation of p27(Kip1) a
t both the mRNA and protein levels. (C) 1998 Academic Press.