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This UPR pathway is mainly initiated by ER stress sensors: PERK, ATF6 and IRE1, and the PERK-eIF2[alpha] and IRE1-TNF receptor-associated factor 2 (TRAF2)-Jun N-terminal kinase (JNK) pathways are the leading regulators for autophagy induction.
Heat induces the splicing by IRE1 of a mRNA encoding a transcription factor involved in the unfolded protein response in Arabidopsis.
4A and B, AB23 obviously induced up-regulation of IRE1[alpha] and Bip in a dose- and time-dependent manner while it didn't affect the eIF2a phosphorylation, indicating that AB23 might activate the IRE1 pathway in the ovarian cancer A2780 and HEY cell lines.
ER stress signaling is mediated through IRE1, a transmembrane kinase/endonuclease that can perceive the accumulation of malfolded peptides in the ER lumen and in turn, catalyze unconventional, cytoplasmic splicing of an mRNA for bZIP60 transcription factor and its translation into a transcriptionally active form that promotes the expression of multiple ER stress-responsive genes.
A component of the UPR known as the IRE1 pathway has generally been thought to handle the protective aspects of this response, promoting cell survival by providing cells with the biological resources they need to cope with stress, while a complementary pathway, called PERK, has been associated with cell death.
Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1.
La proteina IRE1 induce la activacion de la quinasa JNK, que fosforila a las proteinas Bcl-2 y BH3, con la consecuente activacion de BH3 e inactivacion de Bcl-2, lo que promueve la apoptosis (91-93).
The pre-clinical study, conducted by researchers at Dana-Farber Cancer Institute in collaboration with MannKind Corporation (Nasdaq: MNKD), confirm that blocking the XBP1 arm of the unfolded protein response with MannKind's novel, first-in-class IRE1 RNase domain inhibitor, MKC-3946, alone or in combination with bortezomib or 17AAG, inhibited growth in multiple myeloma cells, while leaving normal cells intact.
Objective: The overarching objective of this Interfere to Suppress or Promote IRE1 (INSPIRED) RISE programme is to drive research and innovation in cell stress and drug development for cancer and neurodegenerative diseases by forming an interdisciplinary and intersectoral network of experts with strong, dynamic and productive interactions.
IRE1 represents a strong homeostatic transcription factor.
Molecular cloning of the IRE1 gene encoding ER stress sensor Ire1p
This suggests that IRE1 plays a dual role in pro-survival defense signaling independent of bZIP60.
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