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Regulated degradation of the inner nuclear membrane protein SUN2 maintains nuclear envelope architecture and function

Authors :
Logesvaran Krshnan
Wingyan Skyla Siu
Michael Van de Weijer
Daniel Hayward
Elena Navarro Guerrero
Ulrike Gruneberg
Pedro Carvalho
Source :
eLife, Vol 11 (2022)
Publication Year :
2022
Publisher :
eLife Sciences Publications Ltd, 2022.

Abstract

Nuclear architecture and functions depend on dynamic interactions between nuclear components (such as chromatin) and inner nuclear membrane (INM) proteins. Mutations in INM proteins interfering with these interactions result in disease. However, mechanisms controlling the levels and turnover of INM proteins remain unknown. Here, we describe a mechanism of regulated degradation of the INM SUN domain-containing protein 2 (SUN2). We show that Casein Kinase 2 and the C-terminal domain Nuclear Envelope Phosphatase 1 (CTDNEP1) have opposing effects on SUN2 levels by regulating SUN2 binding to the ubiquitin ligase Skp/Cullin1/F-BoxβTrCP (SCFβTrCP). Upon binding to phosphorylated SUN2, SCFβTrCP promotes its ubiquitination. Ubiquitinated SUN2 is membrane extracted by the AAA ATPase p97 and delivered to the proteasome for degradation. Importantly, accumulation of non-degradable SUN2 results in aberrant nuclear architecture, vulnerability to DNA damage and increased lagging chromosomes in mitosis. These findings uncover a central role of proteolysis in INM protein homeostasis.

Details

Language :
English
ISSN :
2050084X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.8c749268f764f83b1beb1a5d074c12d
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.81573