RRC ID 5925
著者 Alam H, Williams TW, Dumas KJ, Guo C, Yoshina S, Mitani S, Hu PJ.
タイトル EAK-7 controls development and life span by regulating nuclear DAF-16/FoxO activity.
ジャーナル Cell Metab
Abstract FoxO transcription factors control development and longevity in diverse species. Although FoxO regulation via changes in its subcellular localization is well established, little is known about how FoxO activity is regulated in the nucleus. Here, we show that the conserved C. elegans protein EAK-7 acts in parallel to the serine/threonine kinase AKT-1 to inhibit the FoxO transcription factor DAF-16. Loss of EAK-7 activity promotes diapause and longevity in a DAF-16/FoxO-dependent manner. Whereas akt-1 mutation activates DAF-16/FoxO by promoting its translocation from the cytoplasm to the nucleus, eak-7 mutation increases nuclear DAF-16/FoxO activity without influencing DAF-16/FoxO subcellular localization. Thus, EAK-7 and AKT-1 inhibit DAF-16/FoxO activity via distinct mechanisms. Our results implicate EAK-7 as a FoxO regulator and highlight the biological impact of a regulatory pathway that governs the activity of nuclear FoxO without altering its subcellular location.
巻・号 12(1)
ページ 30-41
公開日 2010-7-7
DOI 10.1016/j.cmet.2010.05.004
PII S1550-4131(10)00157-9
PMID 20620993
PMC PMC2907918
MeSH Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism* Forkhead Transcription Factors / metabolism* Longevity Mutation Proto-Oncogene Proteins c-akt / genetics Proto-Oncogene Proteins c-akt / metabolism RNA Interference Transcription Factors / metabolism*
IF 21.567
引用数 31
WOS 分野 ENDOCRINOLOGY & METABOLISM CELL BIOLOGY
リソース情報
線虫 tm3188 tm2447