IndraLab

Statements

USP4 is phosphorylated. 53 / 53
| 48 5
sparser
"The AKT-mediated phosphorylation of USP4 also affects its stability and DUB activity."
25007997
sparser
"This implies that localized PKA phosphorylates USP4."
40449590
sparser
"Elevated levels of phospho-USP4 in post myocardial infraction tissue may represent a cardioprotective event to reduce ubiquitin on sarcomere proteins."
40449590
sparser
"Antibodies against the pSer 829 motif show that adrenergic stimulation enhances phosphorylation of USP4 in mouse adult cardiomyocytes."
40449590
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
sparser
"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
rlimsp
"Phosphorylation of USP15 and USP4 Regulates Localization and Spliceosomal Deubiquitination."
31330151
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."
39623377
sparser
"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
"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
sparser
"The influence of AKAP18 on USP4 phosphorylation was established by RNA knockdown ( xref F , bottom panel)."
40449590
sparser
"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
rlimsp
"Growth factors regulate Rheb ubiquitination through USP4 phosphorylation."
30514904
sparser
"Thus, phosphorylation of sarcoplasmic USP4 may be a cardioprotective response."
40449590
sparser
"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
sparser
"However, AKT-mediated USP4 phosphorylation promoted its subcellular localization to the membrane, where USP4 deubiquitinated TβRI."
24239264
sparser
"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
sparser
"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
sparser
"This highlights the potential therapeutic role of USP4 phosphorylation in tumour progression ( xref ; xref )."
34177595
sparser
"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
sparser
"That study suggested a model where PI3K/AKT activation induced phosphorylated USP4 to relocate and stabilize TβRI in the plasma membrane."
24239264
sparser
"In situ detection of phospho-Ser 829 on USP4."
40449590
sparser
"First, data presented in xref show that gene silencing of AKAP18 reduces cAMP responsive phosphorylation of USP4."
40449590
sparser
"Cell-based evaluation of USP4 phosphorylation was conducted in two ways."
40449590
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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
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
sparser
"Alternatively, increased detection of phospho-USP4 in human post MI tissue ( xref J ) may be a consequence of elevated PKA activity that occurs as a response to arterial blockage ( xref )."
40449590
sparser
"They further showed that USP4 could interact with Akt at endogenous level, and phosphorylate USP4 in vitro and in vivo."
28425962
sparser
"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
"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
sparser
"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
sparser
"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
sparser
"The authors also observed phosphorylation of endogenous USP4 upon the addition of TGF-β."
28425962
sparser
"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
sparser
"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
rlimsp
"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
rlimsp
"EGF enhances the deubiquitination of Rheb through AKT-dependent USP4 phosphorylation, leading to the release of Rheb from the TSC complex."
30514904
rlimsp
"Despite the proposed facultative role of this alternatively spliced exon16, the majority of conserved phosphorylation sites in USP4 are within E7, suggesting the protein isoforms may be differently regulated17."
26833277
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
sparser
"Phosphorylated USP4 stabilizes TßRI in the plasma membrane, and thereby enhances TGF-induced protumorigenic effects in cancer cells."
40624457
sparser
"Other evidence suggests that AKT-mediated USP4 phosphorylation leads to the release of RHEB from the TSC complex, which promotes its ubiquitination."
40624457
sparser
"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
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
sparser
"It has been reported that growth factor could induce the phosphorylation of USP4 by AKT xref ."
30514904
sparser
"Growth factors regulate Rheb ubiquitination through USP4 phosphorylation."
30514904
sparser
"We reasoned that incorporation within AKAP18-PKA signaling islands could favor phosphorylation of USP4."
40449590
sparser
"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 can facilitate USP4 phosphorylation and stabilization [ xref ]."
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