IndraLab

Statements


USP17L2 is phosphorylated. 27 / 30
| 27 3

sparser
"This suggests that DUB3 phosphorylation catalyzed by CDK4/6 is essential for YAP1 stability in CRC."

sparser
"We then explored the effects of DUB3 phosphorylation by CDK4/6 on YAP1‐driven oncogenic processes."

sparser
"Altogether, these findings demonstrate that DUB3 phosphorylation by CDK4/6 is critical for YAP1‐driven CRC progression."

sparser
"Furthermore, we discover that DUB3 phosphorylation and subsequent activation by CDK4/6 is a key mechanism to elevate YAP1 expressions in CRC."

sparser
"It was also shown that palbociclib did not directly interact with SNAIL1, but instead acted through the phosphorylation of deubiquitinating enzyme 3 (DUB3), which, in turn, downregulates SNAIL1, xref suggesting a new target for palbociclib."

sparser
"In addition, by using a phospho-CK2 substrate antibody, the phosphorylation of DUB3 was observed which was significantly mitigated by pretreatment of CK2 inhibitor Silmitasertib (Fig. xref )."

sparser
"And the phosphorylation of DUB3 by using phospho-CK2 substrate antibody was completely abrogated by the T495A mutant (Fig. xref )."

sparser
"CK2α-mediated phosphorylation of DUB3 promotes YAP1 stability and oncogenic function."

sparser
"The role of CK2α-mediated DUB3 phosphorylation on YAP1 stability and YAP1-dependent malignant processes was next investigated."

sparser
"These results indicate the critical role of CK2α-mediated phosphorylation of DUB3 on the deubiquitination and stabilization of YAP1."

sparser
"The functional consequence of CK2α-mediated DUB3 phosphorylation was further examined."

sparser
"As shown in xref , WT DUB3 was phosphorylated in cells."

sparser
"However, S41A mutation completely abrogated the phosphorylation of DUB3 at this site, indicating the specificity of this antibody."

sparser
"We next tested CDK4/6-mediated phosphorylation of DUB3 in cells."

sparser
"Furthermore, depletion of CDK4 or CDK6 in cells only partially decreased the phosphorylation of DUB3, while double knockdown of CDK4 and CDK6 almost completely abrogated DUB3 phosphorylation ( xref )."

sparser
"Interestingly, CDK1 also phosphorylated DUB3 at Ser41 in vitro and the treatment of Roscovitine could decrease the phosphorylation of DUB3 ( xref )."

sparser
"Moreover, CDK1 regulates DUB3 phosphorylation and BMAL1-UHRF1 pathway to promoter tumor metastasis [ xref , xref ]."

sparser
"CDK4/6 phosphorylates and activates DUB3."

sparser
"The DUB3 D496H mutation occurs at substrate positions +1, potentially disrupting CK2 recognition and leading to impaired phosphorylation of DUB3 (Fig. xref )."

sparser
"These results establish that CDK4/6-mediated phosphorylation of DUB3 is important for DUB3 activity and SNAIL1 stability."

sparser
"In agreement with the recent report that the deubiquitination activity of DUB3 relies on CDK4/6-mediated phosphorylation of DUB3 and this activity is inhibited by the CDK4/6 inhibitor ( xref ), we demonstrated that treatment of mice with the CDK4/6 inhibitor palbociclib largely sensitized DUB3-proficient prostate tumors to JQ1, but the effect of palbociclib was almost completely abolished by DUB3 knockdown."

sparser
"CDK4 also regulates BRD4 protein levels via phosphorylating SPOP and DUB3 that play a role in BRD4 ubiquitination and degradation ( xref ; xref ; xref ; xref )."

sparser
"CDK4/6-mediated phosphorylation of DUB3 promotes YAP1 stability and hepatocellular carcinoma progression."

sparser
"DUB3 phosphorylation was detected in HCT 116 cells using phospho‐CDK substrate antibody, which was significantly reduced upon CDK4/6 depletion and inhibition (Figure  xref )."

sparser
"Our previous study demonstrated that DUB3 was phosphorylated at Ser41 by CDK4/6, promoting cancer metastasis of triple‐negative breast cancer (TNBC). xref We then tested whether CDK4/6 could catalyze the phosphorylation of DUB3 at the same site in CRC cells."

sparser
"Interestingly, abemaciclib dramatically decreased YAP1 protein levels in cells reconstituting DUB3 WT, but had no effect in those with S41A. The effect of DUB3 phosphorylation by CDK4/6 on YAP1 ubiquitination were next assessed."

sparser
"In particular, it has been demonstrated that both these CDKs can bind and phosphorylate the deubiquitinase USP51 and DUB3, to control ZEB1 [ xref ] and SNAIL1 [ xref ] expression, respectively, thereby modulating the metastatic phenotype of cancer cells."