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N‐Glycans in cell survival and death: cross‐talk between glycosyltransferases
Author(s) -
Banerjee Dipak K,
Banerjee Aditi,
Zhang Zhenbo,
Espinoza Lydia A,
Torres Marina,
Placido Jenny S,
Baksi Krishna
Publication year - 2012
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.26.1_supplement.798.4
Subject(s) - tunicamycin , phosphorylation , biology , glycosylation , dephosphorylation , cancer research , angiogenesis , microbiology and biotechnology , glycosyltransferase , n linked glycosylation , apoptosis , unfolded protein response , biochemistry , glycan , glycoprotein , gene , phosphatase
Asparagine‐linked (N‐linked) protein glycosylation is one of the most important protein modifications. Its importance has been realized in cellular processes including neo‐vascularization (i.e., angiogenesis), a process essential for breast tumor progression. Mannosylphopsho dolichol synthase (DPMS) a positive regulator of N‐acetylglucosamiyl 1‐phosphate transferase (GPT) of the N‐glycan pathway is catalytically upregulated by phosphorylation. Conserved phosphorylation motif has been found in Dpm gene cloned from 35 different species. As a result, triggering of intracellular cAMP activates DPMS and increases protein N‐glycosylation which gets translated in increased angiogenesis. This is reproducible in cells overexpressing DPMS. Interestingly, when ER stress is induced with a GPT inhibitor, tunicamycin cells undergo apoptosis due to unfolded protein response (upr). The DPMS activity is abolished at a rate faster than the cell cycle arrest and the induction of apoptosis. DPMS protein or the mRNA remained higher. Additionally, the DPMS mRNA is synthesized and processed. We then hypothesized that DPMS expression would remain high in a double negative breast tumor microvasculature treated with tunicamycin. Analysis of DPMS expression in tumor tissue sections confirms the hypothesis. Supported by Komen for the Cure BCTR06582; and NIH/NCRR/RCMI G12‐RR03035 (KB) grants.