AI Article Synopsis
- DBC1 plays a key role in cell survival and apoptosis regulation, particularly in response to DNA damage.
- Recent findings show that ATM/ATR kinases phosphorylate DBC1 at Thr454, which is important for activating p53 and triggering apoptosis.
- The study reveals that protein phosphatase 4 (PP4) dephosphorylates DBC1, and this process is crucial for managing DNA damage responses, as altering PP4 levels impacts DBC1 phosphorylation and subsequent cell death outcomes.
Article Abstract
Deleted in breast cancer-1 (DBC1) contributes to the regulation of cell survival and apoptosis. Recent studies demonstrated that DBC is phosphorylated at Thr454 by ATM/ATR kinases in response to DNA damage, which is a critical event for p53 activation and apoptosis. However, how DBC1 phosphorylation is regulated has not been studied. Here we show that protein phosphatase 4 (PP4) dephosphorylates DBC1, regulating its role in DNA damage response. PP4R2, a regulatory subunit of PP4, mediates the interaction between DBC1 and PP4C, a catalytic subunit. PP4C efficiently dephosphorylates pThr454 on DBC1 in vitro, and the depletion of PP4C/PP4R2 in cells alters the kinetics of DBC1 phosphorylation and p53 activation, and increases apoptosis in response to DNA damage, which are compatible with the expression of the phosphomimetic DBC-1 mutant (T454E). These suggest that the PP4-mediated dephosphorylation of DBC1 is necessary for efficient damage responses in cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546941 | PMC |
| http://dx.doi.org/10.14348/molcells.2015.0066 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!