| Literature DB >> 26154057 |
Thomas Heimbucher1, Zheng Liu2, Carine Bossard2, Richard McCloskey3, Andrea C Carrano2, Christian G Riedel4, Bogdan Tanasa5, Christian Klammt6, Bryan R Fonslow7, Celine E Riera8, Bjorn F Lillemeier6, Kenneth Kemphues3, John R Yates7, Clodagh O'Shea2, Tony Hunter9, Andrew Dillin10.
Abstract
FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity.Entities:
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Year: 2015 PMID： 26154057 PMCID： PMC4502596 DOI： 10.1016/j.cmet.2015.06.002
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287