IndraLab

Statements


USP28 is phosphorylated. 30 / 30
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sparser
"We also provided evidence that ATM-mediated phosphorylation of USP28 resulted in its disassociation from KLHL2 and UCK1 destabilization."

sparser
"ATM/IR-Dependent Phosphorylation of USP28."

sparser
"We raised antibodies against the phosphoserine 67 and phosphoserine 714 and used them to confirm that endogenous USP28 is phosphorylated in response to IR ( Figure 7 D)."

sparser
"Furthermore, there appears to be a basal level of USP28 phosphorylation even in the absence of IR treatment for Ser67, suggesting the presence of some constitutive ATM signaling, which could contribut[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"ATM-mediated phosphorylation of USP28 and UCK1 has an opposite effect on their association with KLHL2."

sparser
"We then examined the biological significance of ATM-mediated phosphorylation of USP28."

sparser
"These findings suggested that ATM-mediated phosphorylation of USP28 promotes dissociation of USP28 from KLHL2, destabilizing UCK1."

sparser
"Analysis of USP28 phosphorylation levels."

sparser
"In brief, unphosphorylated USP28 requires complex formation with another E3-ligase, such as FBXW7, for substrate recognition, whereas phosphorylated USP28 can interact and deubiquitinate substrates independently of E3-ligases ( xref C)."
| PMC

sparser
"The downstream ATM kinase CHK2 could be a potential candidate to phosphorylates USP28 following DNA damage."
| PMC

sparser
"We compared the differences in USP28 phosphorylation levels between primary tumors and normal tissues by the CPTAC dataset."

sparser
"USP28 is phosphorylated by ataxia-telangiectasia mutated protein (ATM) kinase at residues S67 and S714, which increases its enzymatic activity."

sparser
"The increased basal levels of DNA damage presented in cancer cells could induce phosphorylation of USP28, thereby allowing the stabilization of USP28 substrates independently of E3-ligases in cancer cells."
| PMC

sparser
"USP28 is also phosphorylated by ATR/ATM and is involved in the response to DNA damage by virtue of its ability to deubiquitinate and stabilize FBW7 (see below), the ubiquitin ligase involved in the degradation of the myc transcription factor ( xref )."

sparser
"This indicates that both stabilization pathways (USP28 and Lin28A phosphorylation by MAPK/ERK) can be blocked by RSV to reduce Lin28A protein expression."

sparser
"Inhibition of ATR via VE-821, but not ATM using KU55933, decreased the phosphorylation of USP28 and strongly reduced the DUB activity of USP28, resulting in an overall reduction of USP28 abundance (Fig.  xref )."

sparser
"Our data show that USP28 is phosphorylated in an ATR-dependent manner upon CPPD treatment and argue that phosphorylated USP28 shows higher deubiquitylase activity."

sparser
"Phosphorylation of USP28 upon Cisplatin exposure is required to repair DNA damage in SCC."

sparser
"Upon exposure to CPPD, USP28 was phosphorylated at reduced levels in the knock-in cells compared to wildtype."

sparser
"In this study we showed that USP28 is recruited to sites of cisplatin-induced DNA damage, resulting in an interaction with ATR and phosphorylation of USP28."

sparser
"The subsequent phosphorylation of USP28 resulted in an increased USP28 enzymatic activity and stabilization of USP28 substrates, such as MYC and ∆Np63."

sparser
"A speculative model might be that in response to DNA damage, phosphorylation of USP28 might activate it to deubiquitinate either GATA4 or an associated factor, thereby preventing its recognition by p62 and autophagic degradation, leading to GATA4 stabilization and SASP activation."

sparser
"In response to ionizing radiation, USP28 is phosphorylated in an ATM-dependent manner, potentially providing a mechanism for control of USP28 activity [3] ."

sparser
"USP28 phosphorylation was also observed following DNA damage and was shown to be ATM-dependent."

sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."

sparser
"The USP25 activity may not be affected upon exposure to an inhibitor blocking the phosphorylation of USP28 on serine 67 and serine It could be another therapeutic option to target the binding between ATM and USP28 and reduce the phosphorylation of USP28, thus decreasing its enzymatic activity in cancer cells with increased DNA damage levels."
| PMC

sparser
"Some studies have reported that phosphorylation of USP28 was closely related to the progression of cancer [ xref , xref ]."

sparser
"It is anticipated that these specific antibodies would not only provide further evidence to support the importance of phosphorylation of UCK1 and USP28 in UCK1 degradation mediated by KLHL2, but also help in screening 5'-AZA chemoresistance in clinical practice."

sparser
"USP28 phosphorylation regulates the complex formation of DNA checkpoint proteins and binds to checkpoint proteins 53BP1, Claspin, and MDC1, resulting in repairing DNA damage."

sparser
"However, whether the above two USP28 phosphorylation sites have functional significance in tumor development, the clinical importance of these post-translational modification sites remains to be further investigated."