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The role of O‐ linked‐N‐acetylglucosamine transferase in regulating autophagy (1094.7)
Author(s) -
McLarty Jennifer,
Paterson Andrew,
Chatham John
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1094.7
Subject(s) - autophagy , microbiology and biotechnology , serine , hek 293 cells , cytoplasm , embryonic stem cell , basal (medicine) , threonine , chemistry , function (biology) , cell , phosphorylation , biology , biochemistry , apoptosis , receptor , endocrinology , gene , insulin
OGT catalyzes the addition of β‐N‐acetylglucosamine (O‐GlcNAc) to the hydroxyl group to serine/threonine residues of nuclear and cytoplasmic proteins, which regulates many biological processes critical for normal cell function. Autophagy is a highly conserved cellular self repair and survival mechanism also critical for normal cell function. We have previously reported that increases in cellular O‐GlcNAc levels interfere with autophagic signaling; therefore, we hypothesized that protein O‐GlcNAcylation may also regulate autophagy. O‐GlcNAc turnover was modulated in cultured human embryonic kidney 293 (HEK293) cells by overexpressing either OGT or a dominant negative OGT (dnOGT). Autophagy was induced either by nutrient deprivation (i.e., ND, serum and glucose free media) or rapamycin (RAP, 100 nM) for 3 hours, which was associated with an increase in overall O‐GlcNAc levels as well as O‐GlcNAcylation of Beclin‐1. Overexpressing OGT increased basal O‐GlcNAc levels and was associated with a decrease in the autophagic response in both ND and RAP treatment. Overexpression of dnOGT decreased overall basal O‐GlcNAcylation as well as attenuated the autophagic response in both ND and RAP groups. This study demonstrates that normal O‐GlcNAc cycling may play a critical role in the regulation of autophagy and provides novel mechanism by which changes in cellular O‐GlcNAcylation mediate cell survival responses. Grant Funding Source : Supported by NIH‐NHLBI grant RO1‐HL101192