IndraLab

Statements

USP4 is phosphorylated. 26 / 26
| 24 2
sparser
"They further showed that USP4 could interact with Akt at endogenous level, and phosphorylate USP4 in vitro and in vivo."
28425962
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
"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
"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
"The AKT-mediated phosphorylation of USP4 also affects its stability and DUB activity."
25007997
sparser
"USP4 phosphorylation is an indispensable process leading to the localization of USP4 from nucleus to cytoplasm."
32669974
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
"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
"In addition, cyclin-dependent kinases (CDKs) were also involved in USP4 phosphorylation which can be hampered by purvalanol A, a CDKs inhibitor."
32669974
sparser
"Growth factors regulate Rheb ubiquitination through USP4 phosphorylation."
30514904
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
"The authors also observed phosphorylation of endogenous USP4 upon the addition of TGF-β."
28425962
sparser
"It has been reported that growth factor could induce the phosphorylation of USP4 by AKT xref ."
30514904
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
"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
"A study demonstrated that AKT-mediated phosphorylation of USP4 was associated with poor prognosis in breast cancer patients."
34177595
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
"Phosphorylated USP4 was found in cytoplasm and cell membrane in breast cancer cells."
32669974
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
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
"This highlights the potential therapeutic role of USP4 phosphorylation in tumour progression ( xref ; xref )."
34177595
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
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
"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
"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