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 |