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Proteasome Inhibitors Shorten Replicative Life Span and Induce a Senescent-like Phenotype of Human Fibroblasts by Claudio Torres; Lindsey Lewis; Vincent J. Cristofalo is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Proteasome Inhibitors Shorten Replicative Life Span and Induce a Senescent-like Phenotype of Human Fibroblasts about?

## Abstract The proteasome constitutes the main non‐lysosomal cellular protease activity, and plays a crucial role not only in the disposal of unwanted material, but also in the regulation of numerous cellular processes. Previously, we have reported that during the replicative senescence of WI‐38 fibroblasts there is a significant impairment in proteasome activity, which probably has important implications in the control of MAPK signaling and cellular proliferation. In this study, we report the potential role of the proteasome in the generation of the senescent phenotype in WI‐38 fibroblasts. Our results indicate that inhibition of proteasome activity leads to an impairment in cell proliferation, and a shortening of the life span. The results also indicate that inhibition of the proteasome in young cells induces a premature senescent‐like phenotype, as indicated by the increase in senescence‐associated β‐galactosidase (SA β‐gal) activity and the abundance of both p21 and collagenase mRNAs, as well as a decreased level of EPC‐1 mRNA known markers of cellular senescence, not previously shown to depend on proteasome activity. Together, our results suggest a molecular mechanism for the

Who reads Proteasome Inhibitors Shorten Replicative Life Span and Induce a Senescent-like Phenotype of Human Fibroblasts?

Author

Claudio Torres; Lindsey Lewis; Vincent J. Cristofalo

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0021-9541)

Published

2006

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)