Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex

被引：95

作者：

Ghazi, Arjumand ^{[1
]}

Henis-Korenblit, Sivan ^{[1
]}

Kenyon, Cynthia ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 14期

关键词：

aging; proteasome; ubiquitin; daf-2; insulin;

D O I：

10.1073/pnas.0700638104

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：5947 / 5952

页数：6

共 39 条

[1]

[Anonymous], 1997, C ELEGANS

[2] Proteasomal degradation of the Fox01 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins [J].

Aoki, M ;

Hao, J ;

Vogt, PK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (37) :13613-13617

[3] Regulation of life-span by germ-line stem cells in Caenorhabditis elegans [J].

Arantes-Oliveira, N ;

Apfeld, J ;

Dillin, A ;

Kenyon, C .

SCIENCE, 2002, 295 (5554) :502-505

[4] Rates of behavior and aging specified by mitochondrial function during development [J].

Dillin, A ;

Hsu, AL ;

Arantes-Oliveira, NA ;

Lehrer-Graiwer, J ;

Hsin, H ;

Fraser, AG ;

Kamath, RS ;

Ahringer, J ;

Kenyon, C .

SCIENCE, 2002, 298 (5602) :2398-2401

[5] LIN-23-mediated degradation of β-catenin regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of C elegans [J].

Dreier, L ;

Burbea, M ;

Kaplan, JM .

NEURON, 2005, 46 (01) :51-64

[6] Caretaker or undertaker? The role of the proteasome in aging [J].

Gaczynska, M ;

Osmulski, PA ;

Ward, WF .

MECHANISMS OF AGEING AND DEVELOPMENT, 2001, 122 (03) :235-254

[7] A systematic RNAi screen for longevity genes in C-elegans [J].

Hamilton, B ;

Doug, YQ ;

Shindo, M ;

Liu, WY ;

Odell, I ;

Ruvkun, G ;

Lee, SS .

GENES & DEVELOPMENT, 2005, 19 (13) :1544-1555

[8] New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen [J].

Hansen, M ;

Hsu, AL ;

Dillin, A ;

Kenyon, C .

PLOS GENETICS, 2005, 1 (01) :119-128

[9] daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans [J].

Henderson, ST ;

Johnson, TE .

CURRENT BIOLOGY, 2001, 11 (24) :1975-1980

[10] The ubiquitin system [J].

Hershko, A ;

Ciechanover, A .

ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :425-479

← 1 2 3 4 →