A Systematic Search for Endoplasmic Reticulum (ER) Membrane-associated RING Finger Proteins Identifies Nixin/ZNRF4 as a Regulator of Calnexin Stability and ER Homeostasis
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To identify novel regulators of endoplasmic reticulum (ER)-linked protein degradation and ER function, we determined the entire inventory of membrane-spanning RING finger E3 ubiquitin ligases localized to the ER. We identified 24 ER membrane-anchored ubiquitin ligases and found Nixin/ZNRF4 to be central for the regulation of calnexin turnover. Ectopic expression of wild type Nixin induced a dramatic down-regulation of the ER-localized chaperone calnexin that was prevented by inactivation of the Nixin RING domain. Importantly, Nixin physically interacts with calnexin in a glycosylation-independent manner, induces calnexin ubiquitination, and p97-dependent degradation, indicating an ER-associated degradation-like mechanism of calnexin turnover.
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RNF170 can be added to the list of known mammalian ER membrane E3 ligases.
“RNF170 can thus be added to the list of known mammalian ER membrane E3 ligases (13, 20).”
From RNF170 Protein, an Endoplasmic Reticulum Membrane Ubiquitin Ligase, Mediates Inositol 1,4,5-Trisphosphate Receptor Ubiquitination and Degradation (2011) · cites this paper as [20]
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Joazeiro, C. A. P., & Weissman, A. M. (2000) · Cell · doi:10.1016/s0092-8674(00)00077-5 · Cited by 1,249 · see citing works
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Lu, J. P., Wang, Y., Sliter, D. A., Pearce, M. M. P., & Wojcikiewicz, R. J. H. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.251983 · Cited by 102 · see citing works
- Authors
- Neutzner, A., Neutzner, M., Benischke, A.-S., Ryu, S.-W., Frank, S., Youle, R. J., & Karbowski, M.
- Affiliations
- National Institutes of Health (US)
- University of Basel (CH)
- University of Maryland, Baltimore (US)
- Corresponding author
- Neutzner, Albert
- Karbowski, Mariusz
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 286
- Issue
- 10
- Pages
- 8633-8643
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3048745
- OpenAlex
- W2067630371
- Cited by
- 62
- References
- 1
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 8 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 8
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM083131)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- RING E3 ubiquitin ligase, endoplasmic reticulum membrane protein, calnexin, ER-associated degradation, ER homeostasis, ubiquitination, protein glycosylation
- MeSH terms
- DNA-Binding Proteins, Endoplasmic Reticulum, Glycosylation, HeLa Cells, Humans, Down-Regulation, Calnexin, Protein Stability
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