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Accurate stress response silencing by an E3 ligase complex mutated in neurodegenerative disease

ABSTRACT: Accurate stress response silencing by an E3 ligase complex mutated in neurodegenerative disease

PROVIDER: PRJNA971195 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24492826_1.fastq.gz	Fastqsanger.gz
	SRR24492826_2.fastq.gz	Fastqsanger.gz
	SRR24492827_1.fastq.gz	Fastqsanger.gz
	SRR24492827_2.fastq.gz	Fastqsanger.gz
	SRR24492828_1.fastq.gz	Fastqsanger.gz

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Accurate stress response silencing by an E3 ligase complex mutated in neurodegenerative disease

Project description:Stress response pathways detect and alleviate many adverse conditions to safeguard cell and tissue homeostasis, yet their prolonged activation induces apoptosis and disrupts organismal health. How stress responses are turned off at the right time and place remains poorly understood. Here, we report a ubiquitin-dependent mechanism to silence the cellular response to mitochondrial protein import stress. Critical to this process is the silencing factor of the integrated stress response (SIFI), a large E3 ligase complex mutated in ataxia that degrades both unimported mitochondrial precursors and stress response components. By recognizing bifunctional substrate motifs that equally encode protein localization and stability, the SIFI complex can rapidly turn off a general stress response after a specific stress has been resolved. Pharmacological stress response silencing sustains cell survival even if stress resolution failed, which underscores the importance of signal termination and provides a roadmap for treating neurodegenerative diseases caused bymitochondrial import defects.

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