RRC ID 51338
Author Hall JA, McElwee MK, Freedman JH.
Title Identification of ATF-7 and the insulin signaling pathway in the regulation of metallothionein in C. elegans suggests roles in aging and reactive oxygen species.
Journal PLoS ONE
Abstract It has been proposed that aging results from the lifelong accumulation of intracellular damage via reactions with reactive oxygen species (ROS). Metallothioneins are conserved cysteine-rich proteins that function as efficient ROS scavengers and may affect longevity. To better understand mechanisms controlling metallothionein expression, the regulatory factors and pathways that controlled cadmium-inducible transcription of the C. elegans metallothionein gene, mtl-1, were identified. The transcription factor ATF-7 was identified in both ethylmethanesulfonate mutagenesis and candidate gene screens. PMK-1 and members of the insulin signaling pathway, PDK-1 and AKT-1/2, were also identified as mtl-1 regulators. Genetic and previous results support a model for the regulation of cadmium-inducible mtl-1 transcription based on the derepression of the constitutively active transcription factor ELT-2. In addition, knockdown of the mammalian homologs of PDK1 and ATF7 in HEK293 cells resulted in changes in metallothionein expression, suggesting that this pathway was evolutionarily conserved. The insulin signaling pathway is known to influence the aging process; however, various factors responsible for affecting the aging phenotype are unknown. Identification of portions of the insulin signaling pathway as regulators of metallothionein expression supports the hypothesis that longevity is affected by the expression of this efficient ROS scavenger.
Volume 12(6)
Pages e0177432
Published 2017
DOI 10.1371/journal.pone.0177432
PII PONE-D-16-49607
PMID 28632756
PMC PMC5478092
MeSH Activating Transcription Factors / genetics Activating Transcription Factors / metabolism* Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gene Expression Regulation* HEK293 Cells Humans Insulin / metabolism* Longevity / genetics* Metallothionein / genetics* Mutagenesis Phosphorylation Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism Reactive Oxygen Species / metabolism* Signal Transduction
IF 2.766
Resource
C.elegans tm1770