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Comparative induction of p53‐regulated gene expression by replicative senescence, pharmacological senescence, and DNA damage
Author(s) -
Gorjala Priyatham,
Mohammedabdul Ataur-Rahman,
Gary Ronald K.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.970.1
Subject(s) - senescence , dna damage , biology , microbiology and biotechnology , gene , gene expression , cell cycle , dna , genetics
The p53 transcription factor is activated rapidly in response to DNA damage. Replicative senescence also requires p53 activity, but the transition from a proliferative to a non‐dividing state occurs gradually over a period of weeks in culture. As cells advance towards senescence, p53‐regulated gene products accumulate slowly but steadily. Beryllium salt induces a senescence‐like state without causing DNA damage, so this reagent can be used to activate the senescence‐signaling functions of p53 more rapidly. Human fibroblasts were: (1) exposed to ionizing radiation to elicit DNA damage, (2) exposed to beryllium to elicit pharmacological senescence, or (3) cultured to attain normal senescence. The mRNA levels of senescence or DNA damage response genes were measured in each treatment group. Some p53‐regulated genes, such as the p21 cell cycle inhibitor, were induced to a similar extent by all three treatments. Other genes, such as BTG2 and GDF15, were overexpressed most strongly after pharmacological induction of senescence. These results suggest that the activity of p53 undergoes incremental adjustments when senescence occurs naturally, but that the senescence‐signaling pathway is capable of pronounced acute activation when provided with a suitable pharmacological stimulus. This work is part of a study of cellular radiation responses, supported by the Nevada NASA EPSCoR Program.