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Title of Journal: Mol Cell Biochem

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Abbravation: Molecular and Cellular Biochemistry

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Springer US

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DOI

10.1016/0169-7439(90)80012-u

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1573-4919

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Apollon/Bruce is upregulated by Humanin

Authors: Yuichi Hashimoto Yuji Takeshita Mikihiko Naito Hiroyuki Uchino Masaaki Matsuoka
Publish Date: 2014/08/20
Volume: 397, Issue: 1-2, Pages: 147-155
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Abstract

Humanin a short bioactive peptide inhibits a variety of cell deaths Humaninmediated inhibition of neuronal cell death caused by an Alzheimer’s disease ADlinked mutant gene occurs via binding of Humanin to its heterotrimeric Humanin receptor htHNR which results in the activation of the Janusassociated kinases JAKs and signal transducer and activator and transcription 3 STAT3 signaling pathway A previous study demonstrated that the Humanininduced activation of the htHNR/JAK2/STAT3 signaling pathway leads to increased expression of SH3 domainbinding protein 5 SH3BP5 which is an essential effector of Humanin’s anticell death activity in some cultured neuronal cells However it remains unknown whether SH3BP5 is the sole effector of the Humanin signaling pathway via htHNR/JAKs/STAT3 Here we show that the Humanin signaling pathway via htHNR/JAKs/STAT3 increased the expression levels of mRNA and protein of Apollon/Bruce an unusual member of the inhibitors of apoptosis proteins and that overexpression of Apollon/Bruce inhibits neuronal death caused by a Londontype familial ADlinked mutant V642I of amyloid β precursor protein Overall the results indicate that expression of Apollon/Bruce is upregulated by Humanin and Apollon/Bruce could be an effector of Humanin in a contextdependent mannerThis work was also in part supported by the GrantinAid for Scientific Research B Grant Number 23390059 to MM the ‘‘Promotion of Science and Technology’’ project for private universities with a matching fund subsidy from the Ministry of Education Culture Sports Science and Technology MEXT to MM The GrantinAid for Scientific Research C Grant Number 25460343 to YH We thank Yuka Toyama and Takako Hiraki for technical assistance throughout the study

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