RRC ID 59493
著者 Ganner A, Gerber J, Ziegler AK, Li Y, Kandzia J, Matulenski T, Kreis S, Breves G, Klein M, Walz G, Neumann-Haefelin E.
タイトル CBP-1/p300 acetyltransferase regulates SKN-1/Nrf cellular levels, nuclear localization, and activity in C. elegans.
ジャーナル Exp Gerontol
Abstract SKN-1/Nrf transcription factors regulate diverse biological processes essentially stress defense, detoxification, and longevity. Studies in model organisms have identified a broad range of regulatory processes and mechanisms that profoundly influence SKN-1/Nrf functions. Defining the mechanisms how SKN-1 is regulated will provide insight how cells defend against diverse stressors contributing to aging and disease. In this study, we demonstrate a crucial role for the acetyltransferase CBP-1, the C. elegans homolog of mammalian CREB-binding protein CBP/p300 in the activation of SKN-1. cbp-1 is essential for tolerance of oxidative stress and normal lifespan. CBP-1 directly interacts with SKN-1 and increases SKN-1 protein abundance. In particular CBP-1 modulates SKN-1 nuclear translocation under basal conditions and in response to stress and promotes SKN-1-dependent transcription of protective genes. Moreover, CBP-1 is required for SKN-1 nuclear recruitment, transcriptional activity, and longevity due to reduced insulin/IGF-1-like signaling, mTOR-, and GSK-3 signaling. Our findings establish the acetyltransferase CBP-1 as a critical activator of SKN-1 that directly modulates SKN-1 protein stability, nuclear localization, and function to ascertain normal stress response and lifespan.
巻・号 126
ページ 110690
公開日 2019-10-15
DOI 10.1016/j.exger.2019.110690
PII S0531-5565(19)30314-6
PMID 31419472
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caenorhabditis elegans Proteins / physiology* Cell Nucleus / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Gene Expression Regulation / physiology Histone Acetyltransferases / physiology* Longevity / physiology Oxidative Stress / physiology Transcription Factors / genetics Transcription Factors / metabolism* Transcription Factors / physiology* p300-CBP Transcription Factors / physiology*
IF 3.08
引用数 3
リソース情報
線虫 tm1817