Apollon/Bruce is upregulated by Humanin

Mol Cell Biochem. 2014 Dec;397(1-2):147-55. doi: 10.1007/s11010-014-2182-4. Epub 2014 Aug 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cells, Cultured
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Inhibitor of Apoptosis Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / pharmacology*
  • Janus Kinases / genetics
  • Janus Kinases / metabolism
  • Mice
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics

Substances

  • BIRC6 protein, human
  • BIRC6 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Intracellular Signaling Peptides and Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • humanin
  • Janus Kinases