IndraLab

Statements

USP20 is phosphorylated. 37 / 37
| 23 14
rlimsp
"As shown in Figure 5D and Supplementary Figure S4C, ATR depletion compromised USP20 phosphorylation at the SQ/TQ motifs and resulted in USP20 downregulation, suggesting that ATR is the major kinase responsible for USP20 phosphorylation and upregulation following replication stress."
25355518
sparser
"Upon replication stress, ATR-mediated phosphorylation of USP20 promotes dissociation of HERC2 from USP20, stabilizes USP20 and its association with CLASPIN, thus increasing CALSPIN stability and ensuring CHK1 activation."
25326330
sparser
"USP20 phosphorylation by ATR does not affect its E3 ligase activity per se , suggesting that USP20 levels, but not catalytic activity, are subjected to ATR regulation."
25355518
sparser
"As shown in Figure xref and Supplementary Figure S4C, ATR depletion compromised USP20 phosphorylation at the SQ/TQ motifs and resulted in USP20 downregulation, suggesting that ATR is the major kinase responsible for USP20 phosphorylation and upregulation following replication stress."
25355518
sparser
"Similar to other DNA repair proteins, USP20 is phosphorylated post DNA damage, and its depletion sensitizes cancer cells to damaging agents that form blocks ahead of the replication forks."
24923443
rlimsp
"We found that individual mutation at these sites partially affected USP20 phosphorylation, while mutating all four sites (4 mut) abolished USP20 phosphorylation (Figure 5E and F)."
25355518
sparser
"This occurred in a phosphorylation-dependent manner, because only the non-phosphorylated USP20 was active."
26445063
sparser
"These suggest that ATR-mediated phosphorylation of USP20 promotes dissociation of USP20 from HERC2, and this dissociation would stabilize CLASPIN and promote CHK1 activation."
25326330
sparser
"Under replication stress, ATR-mediated phosphorylation of USP20 results in the disassociation of HERC2 from USP20."
25326330
rlimsp
"(D) USP20 was phosphorylated on its S/TQ motifs. 293T cells were transfected with FLAG-VEC, FLAG-USP20 or FLAG-USP20(4SA), in which all the four S/TQ sites within the USP20 polypeptide were mutated to AQ."
25326330
rlimsp
"Our findings reveal a dynamic regulation of USP20 by site-specific phosphorylation as well as the interdependence of signal transduction and trafficking pathways in balancing adrenergic stimulation and maintaining cellular homeostasis."
25666616
sparser
"Since ATR is a major kinase activated by replication stress, we further confirmed the role of ATR in USP20 phosphorylation using cells depleted of ATR by shRNA."
25355518
sparser
"These results suggest that ATR-mediated phosphorylation of USP20 is required for USP20 stabilization through inducing disassociation of HERC2 and USP20."
25355518
sparser
"We then wanted to determine the biological function of ATR-mediated phosphorylation of USP20."
25326330
rlimsp
"Furthermore, USP20 phosphorylation increased at the early time point in response to UV treatment and decreased when the cells were recovered from DNA damage (Supplementary Figure S4B)."
25355518
sparser
"Besides, ATR phosphorylates and also stabilizes USP20 by unbinding it from HERC2."
31447701
rlimsp
"One is that USP20 phosphorylation itself affects the binding between USP20 and HERC2."
25355518
sparser
"Currently, we do not know how USP20 phosphorylation affects its binding to HERC2."
25355518
sparser
"One is that USP20 phosphorylation itself affects the binding between USP20 and HERC2."
25355518
rlimsp
"Under replication stress, ATR-mediated phosphorylation of USP20 results in the disassociation of HERC2 from USP20."
25326330
sparser
"Furthermore, USP20 phosphorylation increased at the early time point in response to UV treatment and decreased when the cells were recovered from DNA damage (Supplementary Figure S4B)."
25355518
sparser
"There are four potential SQ/TQ motifs in USP20: T170Q, T232Q, S305Q and S662Q. We found that individual mutation at these sites partially affected USP20 phosphorylation, while mutating all four sites (4 mut) abolished USP20 phosphorylation (Figure xref and xref )."
25355518
rlimsp
"Currently, we do not know how USP20 phosphorylation affects its binding to HERC2."
25355518
sparser
"Additionally, β1AR-induced USP20 phosphorylation may serve as a feed-forward mechanism to stabilize β1AR expression and signaling during pathological insults to the myocardium."
30538132
sparser
"Using an antibody against consensus ATM/ATR phosphorylation sites (anti-phospho-SQ/TQ), we found that phosphorylation of USP20 at SQ/TQ motifs following HU or UV treatment and USP20 phosphorylation was blocked by caffeine (Figure xref and xref )."
25355518
rlimsp
"Similar to other DNA repair proteins, USP20 is phosphorylated post DNA damage, and its depletion sensitizes cancer cells to damaging agents that form blocks ahead of the replication forks."
24923443
sparser
"USP20 phosphorylation by ATR is important for its stabilization and checkpoint activation."
25355518
sparser
"Phospho-USP20 was undetectable in β1AR KO mice subjected to TAC, suggesting a role for USP20 phosphorylation in cardiac response to pressure overload."
30538132
sparser
"The other possibility is that USP20 phosphorylation changes USP20 conformation, which in turn prevents HERC2 binding."
25355518
rlimsp
"ATR-mediated phosphorylation of USP20 promotes its dissociation from HERC2."
25326330
rlimsp
"These suggest that ATR-mediated phosphorylation of USP20 promotes dissociation of USP20 from HERC2, and this dissociation would stabilize CLASPIN and promote CHK1 activation."
25326330
rlimsp
"Upon replication stress, ATR-mediated phosphorylation of USP20 promotes dissociation of HERC2 from USP20, stabilizes USP20 and its association with CLASPIN, thus increasing CALSPIN stability and ensuring CHK1 activation."
25326330
rlimsp
"We then wanted to determine the biological function of ATR-mediated phosphorylation of USP20."
25326330
sparser
"This study reveals an unexpected regulatory axis from mTORC1 to HMGCR via USP20 phosphorylation and suggests that inhibitors of USP20 could be used to lower cholesterol levels to treat metabolic diseases including hyperlipidaemia, liver steatosis, obesity and diabetes."
33177714
sparser
"ATR-mediated phosphorylation of USP20 promotes its dissociation from HERC2."
25326330
rlimsp
"Since ATR is a major kinase activated by replication stress, we further confirmed the role of ATR in USP20 phosphorylation using cells depleted of ATR by shRNA."
25355518
sparser
"These results establish the important role of USP20 phosphorylation in ATR-dependent DDR."
25355518