Ubiquitin specific protease 4 positively regulates the WNT/β‐catenin signaling in colorectal cancer

Yun, Sun-Il; Kim, Hyeon Ho; Yoon, Jung Hwan; Park, Won Sang; Hahn, Myong‐Joon; Kim, Hee Cheol; Chung, Chin Ha; Kim, Kyeong Kyu

doi:10.1016/j.molonc.2015.06.006

Cited by 94 publications

(90 citation statements)

References 44 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRABID also positively regulates Wnt signaling by deubiquitylating adenomatous polyposis coli (APC) and regulating the stability of the β-catenin/ TCF transcription complex (18). USP47 and USP4 can directly regulate β-catenin deubiquitylation (19,20). USP8 deubiquitylates endosome-tethered Fzd, resulting in the recycling of Fzd to the plasma membrane (21).…”

mentioning

confidence: 99%

USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds

Madan

Walker

Young

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The Wnt signaling pathways play pivotal roles in carcinogenesis. Modulation of the cell-surface abundance of Wnt receptors is emerging as an important mechanism for regulating sensitivity to Wnt ligands. Endocytosis and degradation of the Wnt receptors Frizzled (Fzd) and lipoprotein-related protein 6 (LRP6) are regulated by the E3 ubiquitin ligases zinc and ring finger 3 (ZNRF3) and ring finger protein 43 (RNF43), which are disrupted in cancer. In a genome-wide small interfering RNA screen, we identified the deubiquitylase ubiquitin-specific protease 6 (USP6) as a potent activator of Wnt signaling. USP6 enhances Wnt signaling by deubiquitylating Fzds, thereby increasing their cell-surface abundance. Chromosomal translocations in nodular fasciitis result in USP6 overexpression, leading to transcriptional activation of the Wnt/β-catenin pathway. Inhibition of Wnt signaling using Dickkopf-1 (DKK1) or a Porcupine (PORCN) inhibitor significantly decreased the growth of USP6-driven xenograft tumors, indicating that Wnt signaling is a key target of USP6 during tumorigenesis. Our study defines an additional route to ectopic Wnt pathway activation in human disease, and identifies a potential approach to modulate Wnt signaling for therapeutic benefit.

show abstract

mentioning

confidence: 99%

USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds

Madan

Walker

Young

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Ubiquitin specific peptidase 4 function is important during tumorigenesis because this deubiquitinating enzyme has a key role in the regulation of TP53 and TGFβ signaling and is also a positive regulator of the WNT/β-catenin signaling [18][19][20]. Deubiquitinating enzyme UPS10 suppresses the proliferation and growth of cancer cells through stabilization of p53 protein [21].…”

mentioning

confidence: 99%

Expression of ubiquitin specific peptidase and ATG7 genes in U87 glioma cells upon glutamine deprivation

Halkin¹,

Minchenko²,

Riabovol³

et al. 2017

Ukr.Biochem.J

View full text Add to dashboard Cite

We have studied the effect of glutamine deprivation on the expression of genes encoding for ubiquitin specific peptidases (usP) [4][5][6]. A better knowledge of tumor respon ses to glutamine deprivation condition is required to elaborate new therapeutical strategies of cell sensibilization, based on the blockade of survival mechanisms.Ubiquitin is a highly conserved protein involved in regulation of intracellular protein breakdown, cell cycle regulation, chromatin remodeling, and stress response. It is released from degraded proteins by disassembly of the polyubiquitin chains, which is mediated by ubiquitin-specific proteases, members of the ubiquitin-specific processing family of proteases for deubiquitination of proteins [7][8][9]. E3 ubiquitin ligases and deubiquitylases play an important role in cancer [7,10,11]. Our previous results demonstrated possible interaction/cross-talk between unfolding protein response signaling and ubiquitin system during adjustment to episodes of hypoxia during tumor development [12]. Ubiquitin specific peptidases (USPs) and ubiquitin activating enzyme E1-like protein/autophagy related 7 (GSA7/ ATG7) are involved in cancer cells survival and progression [13][14][15]. USP1 and USP7 are responsible for deubiquitination of mono-ubiquitinated PCNA (proliferating cell nuclear antigen), which activates error-prone DNA polymerases and controls an oxidative-stress-induced mutagenesis in human cells [13]. Decreased levels of USP1 in cancer cells have been implicated in lung and glioblastoma tumors growth and progression [14,16]. There is data that serine phosphorylation is critical for the activity of USP1 and its interaction with WD40-repeat protein UAF1; while two nuclear localization signals

show abstract

“…USP4 overexpression is correlated with numerous types of cancer because it deubiquitinates ubiquitin-conjugated proteins. Wnt/b-catenin signalling is a significant pathway in osteoblast differentiation and is also modulated by USP4 [62,63]. USP4 affects neuronal apoptosis in the intracerebral hemorrhage pathway [53], which could be correlated with human breast cancer migration and invasion by promoting relaxin/transforming growth factor-b1/ Smad2/matrix metallopeptidase 9 signalling [54], and also modulates the activation of transforming growth factor b-activated kinase 1-(JNK1/2)/p38 signalling in cardiac hypertrophy [55].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, USP4 has important roles in DNA-end resection and DNA repair [4], p53 and NF-jB signalling [59], homologous recombination [60] and DNA double-strand breaks [61]. Wnt/b-catenin signalling is a significant pathway in osteoblast differentiation and is also modulated by USP4 [62,63]. Recently, it was found that USP4 interacts with programmed cell death 4, thereby repressing cell proliferation in breast cancer cells [64].…”

Section: Discussionmentioning

confidence: 99%

RNPS1 is modulated by ubiquitin‐specific protease 4

2017

View full text Add to dashboard Cite

RNA-binding protein with serine-rich domain 1 (RNPS1) is a component of pre-splicing and post-splicing multiprotein complexes, which activates constitutive and alternative splicing. RNPS1 participates in the formation of the spliceosome and activates the pre-mRNA splicing process. In the present study, we found that ubiquitin-specific protease 4 (USP4) is a binding partner of RNPS1. Although RNPS1 is polyubiquitinated by both K48- and K63-linkages, USP4 exclusively deubiquitinates K63-linked polyubiquitin chains of RNPS1. We also demonstrate that the catalytic activity of USP4 on ubiquitinated RNPS1 is elevated by squamous cell carcinoma antigen recognized by T cells 3 (Sart3).

show abstract

Ubiquitin specific protease 4 positively regulates the WNT/β‐catenin signaling in colorectal cancer

Cited by 94 publications

References 44 publications

USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds

USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds

Expression of ubiquitin specific peptidase and ATG7 genes in U87 glioma cells upon glutamine deprivation

RNPS1 is modulated by ubiquitin‐specific protease 4

Contact Info

Product

Resources

About