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ZFP36L2 is a cell cycle-regulated CCCH protein necessary for DNA lesion-induced S-phase arrest

Authors :
Tohru Natsume
Naoto Yokota
Aya Noguchi
Tomohisa Hatta
Shungo Adachi
Hiroyuki Kawahara
Source :
Biology Open, Biology Open, Vol 7, Iss 3 (2018)
Publication Year :
2018
Publisher :
The Company of Biologists Ltd, 2018.

Abstract

ZFP36L2 promotes the destruction of AU-rich element-containing transcripts, while its regulation and functional significance in cell cycle control are scarcely identified. We show that ZFP36L2 is a cell cycle-regulated CCCH protein, the abundance of which is regulated post-translationally at the respective stages of the cell cycle. Indeed, ZFP36L2 protein was eliminated after release from M phase, and ZYG11B-based E3 ligase plays a role in its polyubiquitination in interphase. Although ZFP36L2 is dispensable for normal cell cycle progression, we found that endogenous ZFP36L2 played a key role in cisplatin-induced S-phase arrest, a process in which the suppression of G1/S cyclins is necessary. The accumulation of ZFP36L2 was stimulated under DNA replication stresses and altered interactions with a subset of RNA-binding proteins. Notably, silencing endogenous ZFP36L2 led to impaired cell viability in the presence of cisplatin-induced DNA lesions. Thus, we propose that ZFP36L2 is a key protein that controls S-phase progression in the case of genome instability.<br />Summary: ZFP36L2 is a cell cycle-regulated RNA-binding protein, the abundance of which is regulated post-translationally. This protein is especially accumulated in and critical for the survival of DNA-damaged cells.

Details

Language :
English
ISSN :
20466390
Volume :
7
Issue :
3
Database :
OpenAIRE
Journal :
Biology Open
Accession number :
edsair.doi.dedup.....48e1a96dab315f0acc00f3fda16c355a