Caveolin-1 expression negatively regulates cell cycle progression by inducing G(0)/G(1) arrest via a p53/p21(WAF1/Cip1)-dependent mechanism.

摘要: Caveolin-1 is a principal component of caveolae membranes in vivo. mRNA and protein expression are lost or reduced during cell transformation by activated oncogenes. Interestingly, the human caveolin-1 gene localized to suspected tumor suppressor locus (7q31.1). However, it remains unknown whether plays any role regulating cycle progression. Here, we directly demonstrate that arrests cells G0/G1 phase cycle. We show serum starvation induces up-regulation endogenous Moreover, targeted down-regulation exit phase. Next, constructed green fluorescent protein-tagged (Cav-1-GFP) examine effect on regulation. recombinant Cav-1-GFP arrest To important for modulating progression vivo, expressed wild-type as transgene mice. Analysis primary cultures mouse embryonic fibroblasts from transgenic mice reveals 1) S with concomitant increase population, 2) reduction cellular proliferation, 3) DNA replication rate. Finally, caveolin-1-mediated occurs through p53/p21-dependent pathway. Taken together, our results provide first evidence critical modulation