Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex

@article{citeulike:1998734, abstract = {The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan. 10.1073/pnas.0700638104}, author = {Ghazi, Arjumand and Henis-Korenblit, Sivan and Kenyon, Cynthia }, citeulike-article-id = {1998734}, doi = {10.1073/pnas.0700638104}, journal = {Proceedings of the National Academy of Sciences}, keywords = {aging, foxo, ubiquitination}, month = {April}, number = {14}, pages = {5947--5952}, posted-at = {2007-11-28 01:35:09}, priority = {5}, title = {Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex}, url = {http://dx.doi.org/10.1073/pnas.0700638104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1998734 L3 - citeulike-article-id:1998734 TI - Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex JF - Proceedings of the National Academy of Sciences VL - 104 IS - 14 SP - 5947 EP - 5952 N2 - The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan. 10.1073/pnas.0700638104 KW - aging KW - foxo KW - ubiquitination AU - Ghazi, Arjumand AU - Henis-Korenblit, Sivan AU - Kenyon, Cynthia PY - 2007/04/03/ UR - http://dx.doi.org/10.1073/pnas.0700638104 ER -