Journal
AUTOPHAGY
Volume 9, Issue 9, Pages 1440-1442Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.25833
Keywords
p53; ChIP-seq; RNA-seq; tumor suppression; autophagy; apoptosis
Categories
Funding
- NCI NIH HHS [R01 CA140875] Funding Source: Medline
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The mechanisms by which the TP53/TRP53 transcription factor acts as a tumor suppressor remain incompletely understood. To gain new insights into TP53/TRP53 biology, we used ChIP-seq and RNA-seq technologies to define global TRP53 transcriptional networks in primary cells subjected to DNA damage. Intriguingly, we identified a TRP53-regulated autophagy program, which can be coordinately regulated by the TRP53 family members TRP63 and TRP73 in certain settings. While autophagy is not involved in TRP53-dependent cell cycle arrest, it contributes to both TRP53-driven apoptosis in response to DNA damage and TRP53-mediated transformation suppression. Collectively, our genome-wide analyses reveal a profound role for TRP53 in regulating autophagy, through an extensive transcriptional network, and have demonstrated an important role for this program in promoting TRP53-mediated apoptosis and tumor suppression.
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