Ubiquitin-dependent and -independent Functions of OTULIN in Cell Fate Control and Beyond

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2020 Dec 8

PMID 33288901

Citations 21

Authors

Nadine Weinelt

Sjoerd J L van Wijk

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

OTULIN confers cisplatin resistance in osteosarcoma by mediating GPX4 protein homeostasis to evade the mitochondrial apoptotic pathway.

Zheng Z, Zeng Y, Bao X, Huang C, Guo F, Xu F J Exp Clin Cancer Res. 2024; 43(1):330.

PMID: 39721999 PMC: 11670407. DOI: 10.1186/s13046-024-03249-8.

The deubiquitinating protein OTUD6B promotes lung adenocarcinoma progression by stabilizing RIPK1.

Yang M, Wei Y, He X, Xia C Biol Direct. 2024; 19(1):46.

PMID: 38880876 PMC: 11181667. DOI: 10.1186/s13062-024-00489-8.

OTULIN haploinsufficiency predisposes to environmentally directed inflammation.

Staels F, Bucken L, De Vuyst L, Willemsen M, Van Nieuwenhove E, Gerbaux M Front Immunol. 2024; 15:983686.

PMID: 38827742 PMC: 11140568. DOI: 10.3389/fimmu.2024.983686.

Caballero-Oteyza A, Crisponi L, Peng X, Wang H, Mrovecova P, Olla S Res Sq. 2024; .

PMID: 38712244 PMC: 11071612. DOI: 10.21203/rs.3.rs-3950863/v2.

Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis.

Fu Y, Li L, Zhang X, Deng Z, Wu Y, Chen W Nat Commun. 2024; 15(1):2974.

PMID: 38582895 PMC: 10998861. DOI: 10.1038/s41467-024-47289-2.

References

Husnjak K, Dikic I . Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu Rev Biochem. 2012; 81:291-322. DOI: 10.1146/annurev-biochem-051810-094654. View

Akutsu M, Dikic I, Bremm A . Ubiquitin chain diversity at a glance. J Cell Sci. 2016; 129(5):875-80. DOI: 10.1242/jcs.183954. View

Boisson B, Laplantine E, Dobbs K, Cobat A, Tarantino N, Hazen M . Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. J Exp Med. 2015; 212(6):939-51. PMC: 4451137. DOI: 10.1084/jem.20141130. View

Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z . Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol. 2012; 13(12):1178-86. PMC: 3514453. DOI: 10.1038/ni.2457. View

Gerlach B, Cordier S, Schmukle A, Emmerich C, Rieser E, Haas T . Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 2011; 471(7340):591-6. DOI: 10.1038/nature09816. View

Ikeda F, Deribe Y, Skanland S, Stieglitz B, Grabbe C, Franz-Wachtel M . SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis. Nature. 2011; 471(7340):637-41. PMC: 3085511. DOI: 10.1038/nature09814. View

Damgaard R, Elliott P, Swatek K, Maher E, Stepensky P, Elpeleg O . OTULIN deficiency in ORAS causes cell type-specific LUBAC degradation, dysregulated TNF signalling and cell death. EMBO Mol Med. 2019; 11(3). PMC: 6404114. DOI: 10.15252/emmm.201809324. View

Damgaard R, Walker J, Marco-Casanova P, Morgan N, Titheradge H, Elliott P . The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity. Cell. 2016; 166(5):1215-1230.e20. PMC: 5002269. DOI: 10.1016/j.cell.2016.07.019. View

Zhou Q, Yu X, Demirkaya E, Deuitch N, Stone D, Tsai W . Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci U S A. 2016; 113(36):10127-32. PMC: 5018768. DOI: 10.1073/pnas.1612594113. View

10.

Clague M, Urbe S, Komander D . Breaking the chains: deubiquitylating enzyme specificity begets function. Nat Rev Mol Cell Biol. 2019; 20(6):338-352. DOI: 10.1038/s41580-019-0099-1. View

11.

Ritorto M, Ewan R, Perez-Oliva A, Knebel A, Buhrlage S, Wightman M . Screening of DUB activity and specificity by MALDI-TOF mass spectrometry. Nat Commun. 2014; 5:4763. PMC: 4147353. DOI: 10.1038/ncomms5763. View

12.

Mevissen T, Hospenthal M, Geurink P, Elliott P, Akutsu M, Arnaudo N . OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Cell. 2013; 154(1):169-84. PMC: 3705208. DOI: 10.1016/j.cell.2013.05.046. View

13.

Faesen A, Luna-Vargas M, Geurink P, Clerici M, Merkx R, van Dijk W . The differential modulation of USP activity by internal regulatory domains, interactors and eight ubiquitin chain types. Chem Biol. 2011; 18(12):1550-61. DOI: 10.1016/j.chembiol.2011.10.017. View

14.

Komander D, Reyes-Turcu F, Licchesi J, Odenwaelder P, Wilkinson K, Barford D . Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep. 2009; 10(5):466-73. PMC: 2680876. DOI: 10.1038/embor.2009.55. View

15.

Sato Y, Goto E, Shibata Y, Kubota Y, Yamagata A, Goto-Ito S . Structures of CYLD USP with Met1- or Lys63-linked diubiquitin reveal mechanisms for dual specificity. Nat Struct Mol Biol. 2015; 22(3):222-9. DOI: 10.1038/nsmb.2970. View

16.

Keusekotten K, Elliott P, Glockner L, Fiil B, Damgaard R, Kulathu Y . OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell. 2013; 153(6):1312-26. PMC: 3690481. DOI: 10.1016/j.cell.2013.05.014. View

17.

Rivkin E, Almeida S, Ceccarelli D, Juang Y, MacLean T, Srikumar T . The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis. Nature. 2013; 498(7454):318-24. PMC: 4931916. DOI: 10.1038/nature12296. View

18.

Schaeffer V, Akutsu M, Olma M, Gomes L, Kawasaki M, Dikic I . Binding of OTULIN to the PUB domain of HOIP controls NF-κB signaling. Mol Cell. 2014; 54(3):349-61. DOI: 10.1016/j.molcel.2014.03.016. View

19.

Elliott P, Nielsen S, Marco-Casanova P, Fiil B, Keusekotten K, Mailand N . Molecular basis and regulation of OTULIN-LUBAC interaction. Mol Cell. 2014; 54(3):335-48. PMC: 4017264. DOI: 10.1016/j.molcel.2014.03.018. View

20.

Elliott P, Komander D . Regulation of Met1-linked polyubiquitin signalling by the deubiquitinase OTULIN. FEBS J. 2015; 283(1):39-53. PMC: 4765238. DOI: 10.1111/febs.13547. View