Abstract:
: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.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Wei W,Hemmer RM,Sedivy JMdoi
10.1128/MCB.21.20.6748-6757.2001subject
Has Abstractpub_date
2001-10-01 00:00:00pages
6748-57issue
20eissn
0270-7306issn
1098-5549journal_volume
21pub_type
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