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Signal amplification is critical for the induction of unfolded protein response ‐mediated apoptosis
Author(s) -
Banerjee Dipak K,
Banerjee Aditi,
Martinez Juan A,
Longas Maria O,
Baksi Krishna,
Kotapadi Ashok,
Prasad Kilari PVRK,
Santiago Jesus
Publication year - 2013
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.27.1_supplement.801.1
Subject(s) - unfolded protein response , tunicamycin , angiogenesis , signal transduction , microbiology and biotechnology , apoptosis , phosphorylation , biology , chemistry , endoplasmic reticulum , cancer research , biochemistry
Angiognesis (proliferation and differentiation of endothelial cells) is essential for normal growth and development as well as for solid tumor progression and metastasis. Our objective is to understand the dynamic relationship between protein N ‐glycosylation and angiogenesis. Using a protein N ‐glycosylation inhibitor we establish that the anti‐angiogenic action of tunicamycin is mediated by ER stress‐coupled unfolded protein response ( upr ). The cells are incapable of forming colonies and exhibited nuclear fragmentation. To evaluate upr ‐mediated programmed cell death is the consequence of a “cellular tsunami”, genome and proteome were analyzed. There is differential expression of 577 genes, and correlation with protein folding dynamics by Raman Spectroscopy exhibited decreased in area at 1672 cm −1 by 41.85% at 3 h and 55.39% at 12 h; at 1684 cm −1 by 20.63% at 3 h and 40.08% at 12 h; and also at 1994 cm −1 by 33.33% at 3 h and 32.92% at 12 h, respectively. The ER resident protein, mannosylphospho dolichol synthase (DPMS) is unable to remain phosphorylated, and loses catalytic activity irrespective of mRNA and protein expression. Thus, newly synthesized protein chains fail to arrange properly into their final secondary and/or tertiary structures, and the random coils they form undergo further degradation. Supported in part by grants from Susan G. Komen for the Cure BCTR0600582 (DKB) and NIH/NIMHD 8G12MD007583 (KB)