The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity
作者： Thomas Heimbucher , Zheng Liu , Carine Bossard , Richard McCloskey , Andrea C. Carrano
DOI: 10.1016/J.CMET.2015.06.002
关键词:
摘要: FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability function unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator IIS, which stabilizes active protein levels and, a consequence, influences functions, such metabolism, stress response, longevity C. elegans. associates with cellulo in vitro. functions deubiquitylase by removing ubiquitin moieties DAF-16, thus counteracting action RLE-1 E3-ubiquitin ligase. Our findings support model promotes response decreased IIS directly modulating its ubiquitylation state, suggesting regulated oscillations play integral role controlling processes metabolism longevity.
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