Surviving death: emerging concepts of RIPK3 and MLKL ubiquitination in the regulation of necroptosis
- Lytic forms of programmed cell death, like necroptosis, are characterised by cell rupture and the release of cellular contents, often provoking inflammatory responses. In the recent years, necroptosis has been shown to play important roles in human diseases like cancer, infections and ischaemia/reperfusion injury. Coordinated interactions between RIPK1, RIPK3 and MLKL lead to the formation of a dedicated death complex called the necrosome that triggers MLKL-mediated membrane rupture and necroptotic cell death. Necroptotic cell death is tightly controlled by post-translational modifications, among which especially phosphorylation has been characterised in great detail. Although selective ubiquitination is relatively well-explored in the early initiation stages of necroptosis, the mechanisms and functional consequences of RIPK3 and MLKL ubiquitination for necrosome function and necroptosis are only starting to emerge. This review provides an overview on how site-specific ubiquitination of RIPK3 and MLKL regulates, fine-tunes and reverses the execution of necroptotic cell death.
Author: | Rebekka KarlowitzORCiDGND, Sjoerd van WijkORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-750636 |
DOI: | https://doi.org/10.1111/febs.16255 |
ISSN: | 1742-4658 |
Parent Title (English): | The FEBS Journal |
Publisher: | Wiley-Blackwell |
Place of publication: | Oxford [u.a.] |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/10/28 |
Date of first Publication: | 2021/10/28 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/08/11 |
Tag: | MLKL; RIPK3; deubiquitinating enzymes; necroptosis; programmed cell death; ubiquitination |
Volume: | 290 |
Issue: | 1 |
Page Number: | 18 |
First Page: | 37 |
Last Page: | 54 |
Note: | The authors acknowledge funding by the Deutsche Forschungsgemeinschaft (WI 5171/1-1 and FU 436/20-1), the Deutsche Krebshilfe (70113680), the Frankfurter Stiftung für krebskranke Kinder and the Eberhard and Hilde Rüdiger Foundation. Open Access funding enabled and organised by Projekt DEAL, Goethe-Universitat Frankfurt am Main. |
HeBIS-PPN: | 51261220X |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie | |
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 |