第173回細胞生物学セミナー／総合生命科学部生命

第173回細胞生物学セミナー
総合生命科学部生命科学セミナー
演者： Dr. Claudio A. Hetz
（University of Chile, Chile / Harvard School of Public Health, USA）
日時： 2016年9月28日（水）16：00～17：30
場所：京都産業大学総合生命科学部15号館1階 15102セミナー室
http://www.kyoto-su.ac.jp/access.html
演題：
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.
世話人：京都産業大学総合生命科学部・永田和宏（075-705-3134）（内線：9537）
共催：武田科学振興財団

Download Report