The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells

Jumpertz, Sandra; Hennes, Thomas; Asare, Yaw; Vervoorts, Jörg; Bernhagen, Jürgen; Schütz, Anke K.

doi:10.1016/j.cellsig.2014.05.013

Cited by 22 publications

(18 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several previous studies have suggested that SIAH1 represses Wnt signaling by targeting β-catenin for degradation through a phosphorylation-independent mechanism (Liu et al 2001;Matsuzawa and Reed 2001;Dimitrova et al 2010;Jumpertz et al 2014;Shin et al 2016), which is inconsistent with our conclusion. Underlying causes of discrepancies are currently unclear.…”

Section: Discussioncontrasting

confidence: 99%

The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation

Ji¹,

Jiang

Jiang³

et al. 2017

Genes Dev.

View full text Add to dashboard Cite

The Wnt/β-catenin signaling pathway plays essential roles in embryonic development and adult tissue homeostasis. Axin is a concentration-limiting factor responsible for the formation of the β-catenin destruction complex. Wnt signaling itself promotes the degradation of Axin. However, the underlying molecular mechanism and biological relevance of this targeting of Axin have not been elucidated. Here, we identify SIAH1/2 (SIAH) as the E3 ligase mediating Wnt-induced Axin degradation. SIAH proteins promote the ubiquitination and proteasomal degradation of Axin through interacting with a VxP motif in the GSK3-binding domain of Axin, and this function of SIAH is counteracted by GSK3 binding to Axin. Structural analysis reveals that the Axin segment responsible for SIAH binding is also involved in GSK3 binding but adopts distinct conformations in Axin/SIAH and Axin/GSK3 complexes. Knockout of SIAH1 blocks Wnt-induced Axin ubiquitination and attenuates Wnt-induced β-catenin stabilization. Our data suggest that Wnt-induced dissociation of the Axin/GSK3 complex allows SIAH to interact with Axin not associated with GSK3 and promote its degradation and that SIAH-mediated Axin degradation represents an important feed-forward mechanism to achieve sustained Wnt/β-catenin signaling.

show abstract

Section: Discussioncontrasting

confidence: 99%

The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation

Ji¹,

Jiang

Jiang³

et al. 2017

Genes Dev.

View full text Add to dashboard Cite

show abstract

“…Previous studies showed β-catenin upregulation in many cancers, including CRC [38], and β-catenin overexpression is associated with worse patient outcomes [39]. We found the β-catenin expression in CRC was consistent with previous studies.…”

Section: Discussionsupporting

confidence: 91%

Reciprocal control of lncRNA-BCAT1 and β-catenin pathway reveals lncRNA-BCAT1 long non-coding RNA acts as a tumor suppressor in colorectal cancer

et al. 2017

View full text Add to dashboard Cite

β-catenin plays a major role in tumor development and progression. The present study found that β-catenin was upregulated in 30 samples of colorectal cancer (CRC) tissue as compared to adjacent non-tumor tissues. Analysis of long non-coding RNA (lncRNA) expression profiles using the GSE18560 and GSE44097 datasets, which were generated via the Affymetrix plus 2.0 microarray platform and downloaded from the GEO database, revealed 20 differentially expressed lncRNAs following β-catenin knockdown. We focused on AK091631, a novel lncRNA, which we named lncRNA-β-catenin associated transcript 1 (LncRNA-BCAT1). lncRNA-BCAT1 expression was decreased in CRC tissues, and was negatively associated with β-catenin in both CRC tissues and cell lines. lncRNA-BCAT1 overexpression suppressed CRC cell growth and invasion by downregulating cyclin D1, c-Myc, and MMP-2. These results suggest that lncRNA-BCAT1 overexpression inhibits CRC cell growth and invasion via Wnt/β-catenin pathway blockade, and that lncRNA-BCAT1 is repressed by Wnt/β-catenin signaling. This evidence suggests that lncRNA-BCAT1 is a tumor suppressor and that lncRNA-BCAT1 may be an effective prognostic biomarker in CRC.

show abstract

“…HUVECs, HAoECs, MAoECs, and BMDMs were stimulated with 20 ng/mL human or mouse TNF-α or 100 ng/mL LPS as indicated. MLN4924 was dissolved as established (81) and used at a concentration of 500 nmol/L for 2-4 h in all experiments.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo

Asare

Ommer-Bläsius

Azombo

et al. 2017

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

Self Cite

View full text Add to dashboard Cite

Constitutive photomorphogenesis 9 (COP9) signalosome 5 (CSN5), an isopeptidase that removes neural precursor cell-expressed, developmentally down-regulated 8 (NEDD8) moieties from cullins (thus termed "deNEDDylase") and a subunit of the cullin-RING E3 ligase-regulating COP9 signalosome complex, attenuates proinflammatory NF-κB signaling. We previously showed that CSN5 is up-regulated in human atherosclerotic arteries. Here, we investigated the role of CSN5 in atherogenesis in vivo by using mice with myeloidspecific Csn5 deletion. Genetic deletion of Csn5 in Apoe −/− mice markedly exacerbated atherosclerotic lesion formation. This was broadly observed in aortic root, arch, and total aorta of male mice, whereas the effect was less pronounced and site-specific in females. Mechanistically, Csn5 KO potentiated NF-κB signaling and proinflammatory cytokine expression in macrophages, whereas HIF-1α levels were reduced. Inversely, inhibition of NEDDylation by MLN4924 blocked proinflammatory gene expression and NF-κB activation while enhancing HIF-1α levels and the expression of M2 marker Arginase 1 in inflammatory-elicited macrophages. MLN4924 further attenuated the expression of chemokines and adhesion molecules in endothelial cells and reduced NF-κB activation and monocyte arrest on activated endothelium in vitro. In vivo, MLN4924 reduced LPS-induced inflammation, favored an antiinflammatory macrophage phenotype, and decreased the progression of early atherosclerotic lesions in mice. On the contrary, MLN4924 treatment increased neutrophil and monocyte counts in blood and had no net effect on the progression of more advanced lesions. Our data show that CSN5 is atheroprotective. We conclude that MLN4924 may be useful in preventing early atherogenesis, whereas selectively promoting CSN5-mediated deNEDDylation may be beneficial in all stages of atherosclerosis.A therosclerosis is the primary cause of cardiovascular diseases. As a chronic inflammatory condition of the vessel wall, atherosclerosis is characterized by endothelial cell activation resulting in the secretion of chemoattractant proteins such as CCL2 and macrophage migration inhibitory factor (MIF) and by increased expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These molecules synergize to sequentially recruit inflammatory cells such as monocytes and T lymphocytes into the vessel wall (1-3).The transcription factor NF-κB plays a crucial role in vascular inflammation and atherogenesis, e.g., by controlling the expression of inflammatory cytokines, chemokines, and adhesion molecules that orchestrate the recruitment and adhesion of leukocytes. Also, numerous genes that regulate differentiation, survival, and proliferation of vascular and immune cells involved in the inflammatory response are targets of NF-κB (4). In resting cells, the NF-κB dimer, p65 and p50, is inactivated by binding to the inhibitor of κB (IκB)-α protein. Inflammatory challenges such as LPS or TNF-α exposure trigg...

show abstract

The β-catenin E3 ubiquitin ligase SIAH-1 is regulated by CSN5/JAB1 in CRC cells

Cited by 22 publications

References 42 publications

The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation

The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation

Reciprocal control of lncRNA-BCAT1 and β-catenin pathway reveals lncRNA-BCAT1 long non-coding RNA acts as a tumor suppressor in colorectal cancer

Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo

Contact Info

Product

Resources

About