p53 Requires the Stress Sensor USF1 to Direct Appropriate Cell Fate Decision


Cancer is a complex disease that is characterized by the sequential accumulation of genetic mutations. Exposure to environmental agents, such as solar ultraviolet, induces such alterations and thus contributes to the development of genomic instability. The tumor suppressor p53 has a central role in orchestrating cellular responses to genotoxic stress. In response to DNA-damage, p53 is stabilized and activated to direct cell fate decisions. Cells in which p53 stabilization is compromised become more vulnerable to mutagenic agents and hence the mutation rate increases, which promotes tumor development. Stabilization of p53 is thus a critical step towards cancer prevention. Using a genetic approach, we demonstrate that the ubiquitous transcription factor Upstream Stimulatory factor 1 (USF1) is required for immediate p53 stabilization and appropriate cell fate decisions following genotoxic stress. Furthermore, we show that this involves a novel function of USF1 that underscores its critical role as a stress sensor. The loss of USF1 expression should thus be considered as a potential initiator of tumorigenesis in the context of environmental insults.


Vyšlo v časopise: p53 Requires the Stress Sensor USF1 to Direct Appropriate Cell Fate Decision. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004309
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004309

Souhrn

Cancer is a complex disease that is characterized by the sequential accumulation of genetic mutations. Exposure to environmental agents, such as solar ultraviolet, induces such alterations and thus contributes to the development of genomic instability. The tumor suppressor p53 has a central role in orchestrating cellular responses to genotoxic stress. In response to DNA-damage, p53 is stabilized and activated to direct cell fate decisions. Cells in which p53 stabilization is compromised become more vulnerable to mutagenic agents and hence the mutation rate increases, which promotes tumor development. Stabilization of p53 is thus a critical step towards cancer prevention. Using a genetic approach, we demonstrate that the ubiquitous transcription factor Upstream Stimulatory factor 1 (USF1) is required for immediate p53 stabilization and appropriate cell fate decisions following genotoxic stress. Furthermore, we show that this involves a novel function of USF1 that underscores its critical role as a stress sensor. The loss of USF1 expression should thus be considered as a potential initiator of tumorigenesis in the context of environmental insults.


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