Abstract

Normal cells in culture invariably undergo senescence, whereby they cease proliferation after a finite number of doublings. Irreversible changes in gene expression occurred in senescent human fetal lung fibroblasts: a non-cell cycle-regulated mRNA was partially repressed; an unusual polyadenylated histone mRNA was expressed; although serum induced c-H- ras , c- myc , and ornithine decarboxylase mRNA normally, ornithine decarboxylase activity was deficient; and serum did not induce mRNA for a replication-dependent histone and for the c- fos proto-oncogene. The loss of c- fos inducibility was the result of a specific, transcriptional block. The results suggest that senescent fibroblasts were unable to proliferate because of, at least in part, selective repression of c- fos ; moreover, the multiple changes in gene expression support the view that cellular senescence is a process of terminal differentiation.

Keywords

Ornithine decarboxylaseBiologyPsychological repressionTranscription (linguistics)Gene expressionMolecular biologyMessenger RNAHistonePolyadenylationCell biologyOrnithine decarboxylase antizymeGeneGeneticsEnzymeBiochemistry

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Publication Info

Year
1990
Type
article
Volume
247
Issue
4939
Pages
205-209
Citations
477
Access
Closed

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Tara Seshadri, Judith Campisi (1990). Repression of c- <i>fos</i> Transcription and an Altered Genetic Program in Senescent Human Fibroblasts. Science , 247 (4939) , 205-209. https://doi.org/10.1126/science.2104680

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DOI
10.1126/science.2104680