IndraLab

Statements

USP4 is phosphorylated. 36 / 41
| 36 5
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"The authors also observed phosphorylation of endogenous USP4 upon the addition of TGF-β."
28425962
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"The AKT-mediated phosphorylation of USP4 also affects its stability and DUB activity."
25007997
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"However, AKT-mediated USP4 phosphorylation promoted its subcellular localization to the membrane, where USP4 deubiquitinated TβRI."
24239264
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"They further showed that USP4 could interact with Akt at endogenous level, and phosphorylate USP4 in vitro and in vivo."
28425962
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"We further showed that the phosphorylation of both USP15 and USP4 is regulated by the activity of CDKs, although a question remains on which CDK, or whether more than one CDK, is required for this pho[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
31330151
sparser
"The phosphorylation of USP4 prolongs its half-life on the plasma membrane, and activates TGF-β cell signalling through binding and deubiquitination of TGF-β receptors, which plays a crucial role in tumour cell migration and metastasis."
34177595
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"Moreover, AKT-mediated USP4 phosphorylation can abolish the ubiquitination of Rheb and then stabilize it, which activate the mechanistic target of rapamycin complex 1-mediated signaling pathways, thus influenced tumor growth [ xref ]."
32669974
sparser
"Direct association of USP4 with TβRI at the plasma membrane and USP4-mediated TβRI deubiquitylation are enhanced in response to Akt activation and Akt-mediated USP4 phosphorylation, and directly oppos[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28552280
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"TGF-β-induced migration of MDA-MB-231 cells is inhibited by USP4 knockdown and PI (3) K–AKT signalling inhibitors, indicating that phosphorylation of USP4 plays a critical role in AKT-mediated breast cancer cell migration ( xref ; xref )."
34177595
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"It has been reported that growth factor could induce the phosphorylation of USP4 by AKT xref ."
30514904
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"For example, phosphorylation of USP4 is essential for protein stability, or for forming a complex with itself or another protein partner such as USP15."
34177595
sparser
"AKT-mediated USP4 phosphorylation was shown to enhance the association of USP4 with TGFβRI at the plasma membrane resulting in TGFβRI deubiquitylation, and directly opposes the TGFβRI ubiquitylation by SMURF2 in association with SMAD7 [ xref ]."
29149681
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"AKT can facilitate USP4 phosphorylation and stabilization [ xref ]."
38134227
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"Nevertheless, further studies are needed to elucidate the regulation of RNA splicing according to the cell cycle by reversible phosphorylation of USP15 or USP4."
31330151
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"However, USP4 is phosphorylated upon IGF-I and TGF-β induction, and depletion of USP4 reduces IGF-I-Myr-AKT-induced migration in MDA-MB-231 breast cancer cells [ xref ]."
33946990
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"This process can be achieved by knockout of caspase‐8 and rescued by MLKL, suggesting the distinct interaction between cell death and ubiquitination. xref A study found that PELI1 can promote K48‐linked ubiquitination of RIP3 on Lys363, leading to proteasomal degradation, thereby inhibiting necroptosis. xref It was also demonstrated that CYLD promotes necroptosis after deubiquitination of RIP1 in necrosomes. xref , xref USP37 can regulate BLM RecQ like helicase deubiquitination and stabilises its expression, thereby maintaining the DNA damage response in BC cells. xref Sun found that USP36 deubiquitinates c‐Myc in the nucleolus and acts downstream of c‐Myc to promote BC proliferation. xref AKT was found to promote nuclear export after phosphorylation of USP4 and removes TβRI ubiquitination, promoting TGFβ ‐induced epithelial‐to‐mesenchymal transition in BC. xref Deubiquitination thus plays a crucial role in the development of BC."
37700495
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"Growth factors can stimulate the PI3K-PDK1-AKT pathway to inhibit the TSC complex, by promoting phosphorylation of USP4, a frequently overexpressed deubiquitinase, which antagonizes the effect of RNF1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37944568
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"This highlights the potential therapeutic role of USP4 phosphorylation in tumour progression ( xref ; xref )."
34177595
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"Phosphorylation of USP4 at the alternate residues, Thr149 and Thr219, is mediated by cyclin-dependent kinases and exerts a negative role in pre-mRNA splicing through blocking USP4 interactions with squamous cell carcinoma antigen recognized by T cells 3 (SART3) ( xref )."
33681193
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"That study suggested a model where PI3K/AKT activation induced phosphorylated USP4 to relocate and stabilize TβRI in the plasma membrane."
24239264
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"USP4 phosphorylation is an indispensable process leading to the localization of USP4 from nucleus to cytoplasm."
32669974
sparser
"Phosphorylated USP4 was found in cytoplasm and cell membrane in breast cancer cells."
32669974
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"A study demonstrated that AKT-mediated phosphorylation of USP4 was associated with poor prognosis in breast cancer patients."
34177595
sparser
"In addition, cyclin-dependent kinases (CDKs) were also involved in USP4 phosphorylation which can be hampered by purvalanol A, a CDKs inhibitor."
32669974
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"However, in response to EGF, Rheb is deubiquitinated through Akt-mediated phosphorylation of the deubiquitinase USP4, which enables Rheb to dissociate from TSC, promoting mTORC1."
31281815
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"Further, a genome-wide gain-of-function study revealed that AKT acts as a kinase for USP4 phosphorylation and phosphorylated USP4 moves into the cytoplasm from the nucleus."
| PMC
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"In breast cancer, USP4 can be phosphorylated by AKT activation, with subsequent relocation to and stabilization of TβRI in the plasma membrane, indicating poor prognosis [ 20 ]."
34144056
sparser
"According to a previous study by Iyengar [ xref ], Akt promotes USP4 to enter the cell membrane and cytoplasm to phosphorylate USP4 and regulate its subcellular localization, and Akt phosphorylation of USP4 occurs by combining with other de-ubiquitinating enzymes (DUBs) to de-ubiquitinate the TGF-β receptor [ xref ]."
32308208
sparser
"Importantly, AKT (also known as protein kinase B), which has been associated with poor prognosis in breast cancer, directly associates with and phosphorylates USP4."
22706160
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"AKT-mediated phosphorylation of USP4 at a consensus motif stabilizes this DUB, which in turn deubiquitinates the TGFβ-induced activated TβRI and leads to the stabilization of downstream activation of phosphorylated SMAD2 and SMAD2/SMAD4 complex formation ( xref )."
28166483
sparser
"AKT-mediated phosphorylation of USP4 prevents its ubiquitination and promotes its accumulation at the plasma membrane, thereby stabilizing transforming growth factor-β receptor and downstream signaling in the regulation of epithelial to mesenchymal transition ( xref )."
35764170
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"As aforementioned, phosphorylated USP4 can relocate from nucleus to cytoplasm or cell membrane where USP4 deubiquitylates TGF-β receptor I (TβRI) and stabilizes its expression to activate TGF-β signaling pathway to induce R-Smads phosphorylation and then R-Smads are imported into the nucleus to regulate targeted genes expression [ xref ]."
32669974
sparser
"The AKT-mediated phosphorylation of USP4, on the other hand, triggers its subcellular localization predominantly in the membrane and cytoplasm, whereas the non-phosphorylated form is mostly condensed into the nucleus [ xref ]."
32512887
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"Upon growth factor stimulation, AKT-mediated phosphorylation of TSC2 and USP4 (ubiquitin-specific peptidase 4) liberates Rheb from TSC inhibition, while PRAS40, regulated by AKT and mTORC1, modulates mTORC1 activity through phosphorylation at specific residues [ xref , xref , xref ]."
39595628
sparser
"Growth factors regulate Rheb ubiquitination through USP4 phosphorylation."
30514904
sparser
"Interestingly, phosphorylated USP4 by AKT enhances the stability of TGF-β receptor type I (TGF-βRI) by preventing its ubiquitination, which is crucial for the activation of downstream TGF-β signaling pathways."
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