P22
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Functional Analysis of Drosophila melanogaster PNGase homolog
Yoko Funakoshi, 1Yuki Negishi, 2Peter Gergen, 2William J. Lennarz, 3, 4Naoyuki Taniguchi, 1, 5Tadashi Suzuki
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Glycometabolome Team., Systems Glycobiology Research Group, RIKEN; 2Stony Brook University, NY, USA;
Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN; 4Department of disease Glycomics,
Research Institute for Microbial Diseases, Osaka University; 5CREST, JST
3
Peptide: N-glycanase (PNGase) is a cytosolic enzyme which deglycosylates the N-linked glycans from
glycoproteins, and conserved among eukaryotes from fungi to mammals. This enzyme has recently been found to
function in the context of ER associated degradation (ERAD) pathway, cleaving off the bulky N-linked glycans
before the glycoproteins efficiently processed by the proteasome(1).
However, the biological significance of the cytosolic PNGase has not still been revealed yet, because no
strong phenotypic consequences were observed for null mutant of Saccharomyces cerevisiae PNG1, and there
have rarely been any other reports on mutant analysis yet. In addition, the PNGase orthologues in higher
eukaryotes have distinct domains that are not found in yeast, so the distinct biochemical properties and the
phenotypic consequences are expected. Thus we introduced various model systems including Drosophila
melanogaster, whose PNGase homolog domain organization is similar to the mammalian one(2).
Currently we are analyzing the Drosophila PNGase homolog by both biochemical and genetic strategies,
aiming for linking the protein functions and the biological significance, deduced from the mutant phenotypes. Our
preliminary experiments suggested that the homolog lacks N-glycanase enzymatic activity, however the deletion
mutants showed severe phenotypes, indicating the fact that fly homolog has important functions other than
deglycosylation activity.
References:
(1) Suzuki, T, Cytoplasmic peptide:N-glycanase and catabolic pathway for free N-glycans in the cytosol., Semin
Cell Dev Biol, 18, 6, 2007
(2) Suzuki, T, Park, H, Lennarz, WJ, Cytoplasmic peptide:N-glycanase (PNGase) in eukaryotic cells: occurrence,
primary structure, and potential functions., FASEB J, 16, 7, 2002