IndraLab

Statements

OTULIN is phosphorylated. 26 / 26
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rlimsp
"Moreover, LUBAC-OTULIN complex formation is regulated by OTULIN phosphorylation in the PIM."
24726323
sparser
"OTULIN is phosphorylated during necroptosis, which is inhibited by the phosphatase DUSP14 to suppress cell death [ xref ]."
33919439
sparser
"Wnt3a treatment induced a decrease of β-catenin linear ubiquitination with much-delayed kinetics (Supplementary Fig.  xref ), which may be due to, at least in part, the lack of OTULIN phosphorylation."
32770022
sparser
"Thus, stimulation-associated tyrosine phosphorylation of OTULIN, including at Tyr56, cannot be responsible for OTULIN’s absence from SCs."
26670046
trips
"ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/beta-catenin activation to enhance drug resistance in breast cancers."
32770022
sparser
"Notably, neither mutation of Tyr56 nor phosphorylation of OTULIN affects the catalytic activity of OTULIN in vitro [ xref , xref ], suggesting that Tyr56 phosphorylation mainly regulates the OTULIN–LUBAC interaction."
33288901
rlimsp
"Interestingly, OTULIN directly interacts with LUBAC, and this interaction is dynamic and can be regulated by OTULIN phosphorylation."
26503766
sparser
"Additionally, DNA damage-induced ABL1/c-Abl (ABL proto-oncogene 1) activation can promote the phosphorylation of OTULIN, which enhances its interaction with β-catenin and promotes the activation of Wnt/β-catenin signalling ( xref ) This mechanism plays a critical role in the triple-negative breast cancer (TNBC) progression, metastasis, and drug resistance to cancer treatments ( xref ; xref ; xref )."
34177595
sparser
"Accordingly, we observed a decrease in linear ubiquitination of β-catenin with comparable kinetics in cells treated with Dox, which correlated with the increase of OTULIN phosphorylation (Fig.  xref )."
32770022
sparser
"DNA damage-activated c-Abl is required for OTULIN phosphorylation."
32770022
sparser
"We speculate that the genotoxic stress-induced OTULIN phosphorylation at Tyr56 may not only increase the interaction between OTULIN and β-catenin but also enhance the LUBAC autoubiquitination and self-inhibition through dissociation from HOIP xref , which render OTULIN highly efficient in promoting β-catenin deubiquitination and stabilization upon DNA damage."
32770022
sparser
"This antibody detected OTULIN phosphorylation in cells exposed to genotoxic drugs, which was abrogated by phosphatase treatment or Tyr56 mutation."
32770022
sparser
"Therefore, targeting OTULIN or OTULIN phosphorylation may serve as an effective strategy for the treatment of patients with TNBC ( xref ; xref )."
34177595
sparser
"This observation was further confirmed by our in vitro c-Abl kinase assay showing that Dox-induced OTULIN phosphorylation was suppressed by inhibiting DNA-PK, which was comparable to that in cells treated with imatinib (Supplementary Fig.  xref )."
32770022
sparser
"Moreover, LUBAC-OTULIN complex formation is regulated by OTULIN phosphorylation in the PIM."
24726323
sparser
"Further investigations are needed to elucidate in more detail the consequence of the OTULIN phosphorylation and how it is regulated."
33473179
sparser
"Consistently, phosphorylation of the equivalent residue in OTULIN abolishes the interaction with HOIP [ xref ]."
27913667
sparser
"We observed OTULIN phosphorylation in the cytoplasm along with increased cytoplasmic c-Abl level at later time points after Dox treatment, suggesting that c-Abl may translocate into the cytoplasm after its nuclear activation upon genotoxic stress and promote OTULIN phosphorylation (Supplementary Fig.  xref and xref )."
32770022
sparser
"OTULIN hyper-phosphorylation promotes necroptosis by locking ring finger protein 31 (RNF31, also known as HOIP) away from the cylindromatosis (CYLD) complex, resulting in altered receptor interacting serine/threonine kinase 1 (RIPK1) ubiquitination."
32944611
sparser
"Interestingly, OTULIN directly interacts with LUBAC, and this interaction is dynamic and can be regulated by OTULIN phosphorylation."
26503766
rlimsp
"Furthermore, while OTULIN and the HOIP PUB domain form a gel filtration‐stable complex in vitro, the majority of OTULIN in cell lysates does not coelute with LUBAC indicating that OTULIN may be phosphorylated in cells, and dephosphorylation of OTULIN in cell extracts led to coelution of OTULIN with LUBAC 71."
26503766
sparser
"For example, OTULIN might be specifically phosphorylated after the recruitment to the TNFR as part of an active exclusion mechanism."
24726327
sparser
"Phosphorylation of OTULIN prevents HOIP binding, whereas unphosphorylated OTULIN is part of the endogenous LUBAC complex."
24726323
sparser
"Furthermore, while OTULIN and the HOIP PUB domain form a gel filtration‐stable complex in vitro , the majority of OTULIN in cell lysates does not coelute with LUBAC indicating that OTULIN may be phosphorylated in cells, and dephosphorylation of OTULIN in cell extracts led to coelution of OTULIN with LUBAC xref ."
26503766
sparser
"To further characterize the OTULIN phosphorylation upon genotoxic treatments, we developed an antibody specifically recognizing Tyr56 phosphorylation of OTULIN (4E−S4G)."
32770022
sparser
"However, a physiological relevance of phosphorylation has not been shown so far nor has a kinase capable of phosphorylating OTULIN been identified."
28446710