p53 engagement is a hallmark of an unfolded protein response in the nucleus of mammalian cells

Published: Jan. 6, 2025

Exposure to exogenous and endogenous stress is associated with the intracellular accumulation of aberrant unfolded misfolded proteins. In eukaryotic cells, protein homeostasis within membrane-bound organelles regulated by specialized signaling pathways, response in endoplasmic reticulum serving as a foundational example. Yet, it unclear if similar surveillance mechanism exists nucleus. Here we leveraged engineered proteins called destabilizing domains acutely expose mammalian cells nuclear- or cytosolic- localized protein. We show that appearance either compartment engages common transcriptional transcription factors Nrf1 Nrf2. Uniquely, only nucleus does activate robust p53-driven transient p53-independent cell cycle delay. These studies highlight distinct effects folding unique quality control environment

Language: Английский

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p53 engagement is a hallmark of an unfolded protein response in the nucleus of mammalian cells

Published: Jan. 6, 2025

Exposure to exogenous and endogenous stress is associated with the intracellular accumulation of aberrant unfolded misfolded proteins. In eukaryotic cells, protein homeostasis within membrane-bound organelles regulated by specialized signaling pathways, response in endoplasmic reticulum serving as a foundational example. Yet, it unclear if similar surveillance mechanism exists nucleus. Here we leveraged engineered proteins called destabilizing domains acutely expose mammalian cells nuclear- or cytosolic- localized protein. We show that appearance either compartment engages common transcriptional transcription factors Nrf1 Nrf2. Uniquely, only nucleus does activate robust p53-driven transient p53-independent cell cycle delay. These studies highlight distinct effects folding unique quality control environment

Language: Английский

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p53 engagement is a hallmark of an unfolded protein response in the nucleus of mammalian cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract Exposure to exogenous and endogenous stress is associated with the intracellular accumulation of aberrant unfolded misfolded proteins. In eukaryotic cells, protein homeostasis within membrane-bound organelles regulated by specialized signaling pathways, response in endoplasmic reticulum serving as a foundational example. Yet, it unclear if similar surveillance mechanism exists nucleus. Here we leveraged engineered proteins called destabilizing domains acutely expose mammalian cells nuclear- or cytosolic- localized protein. We show that appearance either compartment engages common transcriptional transcription factors Nrf1 Nrf2. Uniquely, only nucleus does activate robust p53-driven transient p53-independent cell cycle delay. These studies highlight distinct effects folding unique quality control environment

Language: Английский

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