title: Apollon/Bruce is upregulated by Humanin.
abstract: Humanin, a short bioactive peptide, inhibits a variety of cell deaths. Humanin-mediated inhibition of neuronal cell death, caused by an Alzheimer's disease (AD)-linked mutant gene occurs via binding of Humanin to its heterotrimeric Humanin receptor (htHNR), which results in the activation of the Janus-associated kinases (JAKs) and signal transducer and activator and transcription 3 (STAT3) signaling pathway. A previous study demonstrated that the Humanin-induced activation of the htHNR/JAK2/STAT3 signaling pathway leads to increased expression of SH3 domain-binding protein 5 (SH3BP5), which is an essential effector of Humanin's anti-cell 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 London-type familial AD-linked 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 context-dependent manner.
authors.affiliation: Department of Pharmacology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takeshita
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchino
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuoka
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: C401541:BIRC6 protein, human; C490597:BIRC6 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C427211:humanin; D053612:Janus Kinases