Dr. Claudio A. Hetz（University of Chile, Chile / Harvard School of Public Health, USA）
「HSP47: a novel regulator of the Unfolded Protein Response」
Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling pathway known as the unfolded protein response (UPR). IRE1α is an ER endoribonuclease that operates as a major UPR transducer, determining cell fate under ER stress. IRE1α catalyzes the unconventional splicing of the mRNA encoding the transcription factor XBP1, in addition to control the stability of mRNAs through a process known as regulated IRE1α-dependent decay (RIDD). Using a global proteomic approach followed by functional validation we identified several novel regulators of IRE1α signaling, highlighting the ER chaperone HSP47 as the major hit. Cellular and biochemical characterization revealed that HSP47 instigates IRE1α signaling through a physical interaction. At the molecular level, HSP47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate its oligomerization. The regulation of IRE1α signaling by HSP47 was validated using fly and mouse models of ER stress. We conclude that HSP47 is a novel regulator of IRE1α, fine-tuning the threshold to engage the UPR.
|日 時||2016年9月28日（水） 16:00～17:30（15:45開場）|
|場 所||京都産業大学 15号館1階15102セミナー室|