Role of p14(ARF) in replicative and induced senescence of human fibroblasts.

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 Biol

authors

Wei W,Hemmer RM,Sedivy JM

doi

10.1128/MCB.21.20.6748-6757.2001

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

6748-57

issue

20

eissn

0270-7306

issn

1098-5549

journal_volume

21

pub_type

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