EVI/WLS function is regulated by ubiquitylation and is linked to ER-associated degradation by ERLIN2

Wolf, Lucie; Lambert, Annika; Haenlin, Julie; Boutros, Michael

doi:10.1242/jcs.257790

Cited by 18 publications

(24 citation statements)

References 73 publications

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“…First, Jean‐Paul Vincent (The Francis Crick Institute, UK) discussed mechanisms underlying Wnt gradient formation (McGough et al, 2020). Then, Michael Boutros (German Cancer Research Center, Germany) talked about ERAD‐mediated regulation of Evi/Wls protein, which is specifically involved in secretion of Wnt proteins (Wolf et al, 2021). David M. Virshup (Duke‐NUS Medical School, Singapore) described telocyte‐mediated delivery of Wnt ligands in the intestinal stem cell niche, and Steffen Scholpp (University of Exeter, UK) presented cytoneme‐mediated transport of active Wnt5b/Ror2 complexes in zebrafish (Brunt et al, 2021).…”

Section: Oral Presentationsmentioning

confidence: 99%

Wnt 2022 EMBO | the Company of Biologists workshop and Yamada conference

et al. 2023

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Wnt2022 was held on November 15th-19th, 2022, in Awaji Yumebutai International Conference Center, Hyogo Prefecture, Japan, as an in-person meeting for the first time in last 3 years. Wnt signaling is a highly conserved pathway among various species. Since Wnt1 was discovered in 1982, a number of studies using many model animals and human samples have revealed that Wnt signaling plays crucial roles in embryonic development, tissue morphogenesis, and regeneration, as well as many other physiological and pathological processes. Since the year 2022 marks the 40th anniversary of Wnt research, we aimed to look back at our research progress and discuss the future direction of this field. The scientific program consisted of plenary lectures, invited talks, short talks selected from abstracts, and poster sessions. Whereas several different Wnt meetings have been held almost every year in Europe and the United States, this was the first Wnt meeting convened in Asia. Therefore, Wnt2022 was highly anticipated to bring together leaders and young scientists from Europe, the United States, and especially Asia and Oceania. In fact, 148 researchers from 21 countries attended this meeting. Although there were travel and administrative restrictions due to COVID-19, the meeting was highly successful in enabling face-to-face discussions.

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Section: Oral Presentationsmentioning

confidence: 99%

Wnt 2022 EMBO | the Company of Biologists workshop and Yamada conference

et al. 2023

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“…Interestingly, the level of Evi/Wls is regulated by the ERAD pathway, and the post-translational modification of Wnt controls Evi/Wls stability [128]. In a subsequent study, an RNAi-based screen was use to establish that Evi/Wls quantity control is orchestrated by a consortium of ERAD-associated factors [129].…”

Section: β-Cateninmentioning

confidence: 99%

The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates

Kumari

Brodsky

2021

Biomolecules

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All proteins are subject to quality control processes during or soon after their synthesis, and these cellular quality control pathways play critical roles in maintaining homeostasis in the cell and in organism health. Protein quality control is particularly vital for those polypeptides that enter the endoplasmic reticulum (ER). Approximately one-quarter to one-third of all proteins synthesized in eukaryotic cells access the ER because they are destined for transport to the extracellular space, because they represent integral membrane proteins, or because they reside within one of the many compartments of the secretory pathway. However, proteins that mature inefficiently are subject to ER-associated degradation (ERAD), a multi-step pathway involving the chaperone-mediated selection, ubiquitination, and extraction (or “retrotranslocation”) of protein substrates from the ER. Ultimately, these substrates are degraded by the cytosolic proteasome. Interestingly, there is an increasing number of native enzymes and metabolite and solute transporters that are also targeted for ERAD. While some of these proteins may transiently misfold, the ERAD pathway also provides a route to rapidly and quantitatively downregulate the levels and thus the activities of a variety of proteins that mature or reside in the ER.

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“…The cargoreceptor Evi/Wls is recycled from the plasma to the ER by a retromer-dependent mechanism to be loaded again with WNTs [ 19 , 20 ]. Recently, it has been shown that the abundance of WLS/Evi in the ER is regulated by its ubiquitination and subsequent degradation, thereby restricting the secretion of WNTs (Wolf and Boutros, Development, in press) [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

The Roles of Secreted Wnt Ligands in Cancer

Werner

Boonekamp

Zhan

et al. 2023

IJMS

Self Cite

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Wnt ligands are secreted signaling proteins that display a wide range of biological effects. They play key roles in stimulating Wnt signaling pathways to facilitate processes such as tissue homeostasis and regeneration. Dysregulation of Wnt signaling is a hallmark of many cancers and genetic alterations in various Wnt signaling components, which result in ligand-independent or ligand-dependent hyperactivation of the pathway that have been identified. Recently, research is focusing on the impact of Wnt signaling on the interaction between tumor cells and their micro-environment. This Wnt-mediated crosstalk can act either in a tumor promoting or suppressing fashion. In this review, we comprehensively outline the function of Wnt ligands in different tumor entities and their impact on key phenotypes, including cancer stemness, drug resistance, metastasis, and immune evasion. Lastly, we elaborate approaches to target Wnt ligands in cancer therapy.

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EVI/WLS function is regulated by ubiquitylation and is linked to ER-associated degradation by ERLIN2

Cited by 18 publications

References 73 publications

Wnt 2022 EMBO | the Company of Biologists workshop and Yamada conference

Wnt 2022 EMBO | the Company of Biologists workshop and Yamada conference

The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates

The Roles of Secreted Wnt Ligands in Cancer

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