IRE1 alpha - stress no more!

Thu, 06/12/2014 - 16:37

The unfolded protein response (UPR) is a eukaryotic cell mechanism that copes with ER stress and is initiated by three ER-localized sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 alpha (IRE1 alpha). The UPR-responsive downstream signaling is regulated through the ATF6 and IRE1-XBP1 pathways. UPR serves three important mechanisms: inhibiting protein translation to restore normal cell function; increasing production of protein folding-involved chaperones; and activating misfolded protein ubiquitination for targeting and degradation. When the ER-stress is not appropriately relieved, UPR leads to the fail-safe of apoptosis. IRE1 alpha is a single-pass type I membrane protein within the ER membrane, and is ubiquitously expressed, with high levels particularly in the pancreas. It exhibits autophosphorylation and under ER stress conditions, is ADP-ribosylated by PARP16 – this increases both its kinase and endonuclease activities. IRE1 alpha inactivation in mice results in widespread developmental defects, intra-gestational embryonic lethality.

Western Blot: IRE1 alpha [p Ser724] Antibody Western Blot: IRE1 alpha [p Ser724] Antibody

Chuang’s group used a IRE1 alpha antibody in their ovarian cancer studies aimed at examining the anti-cancer effects of the drug magnolol on HER2 expression1. They found that magnolol blocks HER2-mediated transformation via the PI3K pathway. Immunoprecipitations and western blotting were performed with the IRE1 alpha antibody by Lipson et al to establish IRE1 alpha’s role in insulin biosynthesis, suggesting it could be a potential therapeutic target in the future2.  Further insulin-signaling pathway studies with the IRE1 alpha antibody were able to demonstrate that the receptor for activated C-kinase 1 (RACK1) plays a crucial role in glucose downstream signaling in pancreatic beta cells3. Researchers in Chile studying regulation of autophagy and apoptosis as interconnected homeostatic processes were able to use the IRE1 alpha antibody to show that the Bax inhibitor 1 (BI-1) has a novel function as a stress integrator in both fly and mice model systems4. Data on the effect of ER stress on renal fibrosis and tubular damage is somewhat controversial, but Chiang et al have data suggesting that there is a positive correlation in vivo5. Based on their studies with the IRE1 alpha antibody, they suggest that renal integrity can be restored by blocking ER stress-related apoptosis.

Novus Biologicals offers IRE1 alpha reagents for your research needs including:


  1. 21757288
  2. 16950141
  3. 20103773
  4. 21926971
  5. 21863214

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