Cloning and characterization of the C. elegans gas1 homolog: phas-1.

Among the set of genes expressed during the quiescent G0 phase of the cell cycle (gas genes), gas1 encodes for a GPI anchor protein associated to the plasma membrane, which is able to induce growth arrest when overexpressed in proliferating fibroblasts. In this report we describe the isolation and characterization of a gas1 Caenorhabditis elegans homolog, phas-1, that seems to be transcribed as an operon together with a gene encoding for a protein similar to human acid ceramidases. Phas-1 structure is very similar to its mammalian homolog conserving almost all cysteine residues and it is expressed in the pharynx from its early formation, in the two-fold embryo, until the adult stage. Surprisingly, while phas-1 is expressed in all developmental stages, with the exception of the dauer larva, the ceramidase-like encoding gene, co-expressed in the same operon together with phas-1, is absent in embryos and is very abundantly expressed in the dauer larva. Overexpression of phas-1 in growing NIH3T3 fibroblasts is able to inhibit the S-phase entry in a similar manner as its murine homolog. On the other hand, when phas-1 is overexpressed or ablated in C. elegans, no specific phenotype due to its transcription alteration can be observed, despite its localized expression suggesting a role in pharynx function or development.