Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Human C-terminal binding protein (CtBP)-interacting protein (CtIP) is a central regulator to initiate DNA end resection and homologous recombination (HR). Several studies have shown that post-translational modifications control the activity or expression of CtIP. However, it remains unclear whether and how cells restrain CtIP activity in unstressed cells and activate CtIP when needed. Here, we identify that
USP52
directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically,
USP52
removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition,
USP52
is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of
USP52
. Furthermore, depletion of
USP52
sensitizes cells to
PARP
inhibition in a CtIP-dependent manner in vitro and in vivo. Collectively, our findings reveal the key role of
USP52
and the regulatory complexity of CtIP deubiquitination in DNA repair.
...
PMID:USP52 regulates DNA end resection and chemosensitivity through removing inhibitory ubiquitination from CtIP. 3309 10
