Ubiquitin-dependent and -independent functions of OTULIN in cell fate control and beyond
- Ubiquitination, and its control by deubiquitinating enzymes (DUBs), mediates protein stability, function, signaling and cell fate. The ovarian tumor (OTU) family DUB OTULIN (FAM105B) exclusively cleaves linear (Met1-linked) poly-ubiquitin chains and plays important roles in auto-immunity, inflammation and infection. OTULIN regulates Met1-linked ubiquitination downstream of tumor necrosis factor receptor 1 (TNFR1), toll-like receptor (TLR) and nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) receptor activation and interacts with the Met1 ubiquitin-specific linear ubiquitin chain assembly complex (LUBAC) E3 ligase. However, despite extensive research efforts, the receptor and cytosolic roles of OTULIN and the distributions of multiple Met1 ubiquitin-associated E3-DUB complexes in the regulation of cell fate still remain controversial and unclear. Apart from that, novel ubiquitin-independent OTULIN functions have emerged highlighting an even more complex role of OTULIN in cellular homeostasis. For example, OTULIN interferes with endosome-to-plasma membrane trafficking and the OTULIN-related pseudo-DUB OTULINL (FAM105A) resides at the endoplasmic reticulum (ER). Here, we discuss how OTULIN contributes to cell fate control and highlight novel ubiquitin-dependent and -independent functions.
Author: | Nadine WeineltORCiD, Sjoerd van WijkORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-755578 |
DOI: | https://doi.org/10.1038/s41418-020-00675-x |
ISSN: | 1476-5403 |
Parent Title (English): | Cell death and differentiation |
Publisher: | Nature Publishing Group |
Place of publication: | Houndmills, Basingstoke |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2020/12/07 |
Date of first Publication: | 2020/12/07 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/09/12 |
Volume: | 28 |
Issue: | 2 |
Page Number: | 12 |
First Page: | 493 |
Last Page: | 504 |
HeBIS-PPN: | 513650601 |
Institutes: | Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |