Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans

AUTOR(ES)

Friedman, Lisa

FONTE

The National Academy of Sciences

RESUMO

The genome of Caenorhabditis elegans possesses two genes, dpy-18 and phy-2, that encode α subunits of the enzyme prolyl 4-hydroxylase. We have generated deletions within each gene to eliminate prolyl 4-hydroxylase activity from the animal. The dpy-18 mutant has an aberrant body morphology, consistent with a role of prolyl 4-hydroxylase in formation of the body cuticle. The phy-2 mutant is phenotypically wild type. However, the dpy-18; phy-2 double mutant is not viable, suggesting an essential role for prolyl 4-hydroxylase that is normally accomplished by either dpy-18 or phy-2. The effects of the double mutation were mimicked by small-molecule inhibitors of prolyl 4-hydroxylase, validating the genetic results and suggesting that C. elegans can serve as a model system for the discovery of new inhibitors.

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