Role of p14ARF in Replicative and Induced Senescence of Human Fibroblasts
AUTOR(ES)
Wei, Wenyi
FONTE
American Society for Microbiology
RESUMO
Following a proliferative phase of variable duration, most normal somatic cells enter a growth arrest state known as replicative senescence. In addition to telomere shortening, a variety of environmental insults and signaling imbalances can elicit phenotypes closely resembling senescence. We used p53−/− and p21−/− human fibroblast cell strains constructed by gene targeting to investigate the involvement of the Arf-Mdm2-p53-p21 pathway in natural as well as premature senescence states. We propose that in cell types that upregulate p21 during replicative exhaustion, such as normal human fibroblasts, p53, p21, and Rb act sequentially and constitute the major pathway for establishing growth arrest and that the telomere-initiated signal enters this pathway at the level of p53. Our results also revealed a number of significant differences between human and rodent fibroblasts in the regulation of senescence pathways.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=99853Documentos Relacionados
- Regulation of a Senescence Checkpoint Response by the E2F1 Transcription Factor and p14ARF Tumor Suppressor
- p14ARF expression in invasive breast cancers and ductal carcinoma in situ – relationships to p53 and Hdm2
- Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts
- p14ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes
- Evidence that Replication of the Antitumor Adenovirus ONYX-015 Is Not Controlled by the p53 and p14ARF Tumor Suppressor Genes