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Genetic Analysis of Hypoxia Signaling and Response in C. elegans
Author(s) -
SHEN CHUAN,
POWELLCOFFMAN JO ANNE
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb03222.x
Subject(s) - biology , gene , microbiology and biotechnology , hypoxia (environmental) , mutant , hypoxia inducible factor 1 , signal transduction , genetic screen , hypoxia inducible factors , genetics , regulation of gene expression , oxygen , chemistry , organic chemistry
A bstract : During normal development and homeostasis, animals use cellular and systemic strategies to adapt to changing oxygen levels. In mammals, hypoxic tissues secrete growth factors to induce angiogenesis, and individual cells increase anaerobic metabolism in order to sustain basic cellular functions. Many of these critical responses to decreased oxygen availability are regulated by the hypoxia‐inducible factors, dimeric transcriptional complexes consisting of α and β subunits. HIFα proteins are specialized for hypoxia response, and oxygen levels regulate their stability and activity. The C. elegans hif‐1 gene is orthologous to mammalian HIFα genes, and C. elegans has proven to be a powerful system for the study of hypoxia‐inducible factor regulation and function. Mutants lacking hif‐1 function are viable in normoxic or anoxic conditions, but they cannot adapt to hypoxia. Recent genetic analyses in C. elegans led to the identification of the evolutionarily conserved enzyme that hydroxylates HIFa in an oxygen‐dependent manner. Once modified, HIFα binds the von Hippel‐Lindau tumor suppressor protein and is targeted for proteasomal degradation. Here, we briefly review the characterization of C. elegans hif‐1 and interacting genes, and discuss genetic strategies for studying hypoxia signaling and response.