NM23-H2 involves in negative regulation of Diva and Bcl2L10 in apoptosis signaling

Biochem Biophys Res Commun. 2007 Jul 20;359(1):76-82. doi: 10.1016/j.bbrc.2007.05.090. Epub 2007 May 24.

Abstract

The Bcl-2 family members are evolutionally conserved and crucial regulators of apoptosis. Diva (Boo), an ortholog of Bcl2L10 or Bcl-B, is a member of the Bcl-2 family that has contradictory functions in apoptosis. To understand the signaling mechanisms of Diva, we searched for proteins that interact with Diva using the yeast two-hybrid system. We identified a nucleoside diphosphate kinase isoform, NM23-H2. Here, we show that Diva bound to NM23-H2 in cells in which the transmembrane domain of Diva was required, and both proteins were colocalized in cytoplasm. Of interest, Diva protein level was significantly down-regulated by NM23-H2 as knock down of NM23-H2 restored Diva expression. Overexpression of NM23-H2 induced apoptosis, and the depletion of NM23-H2 led to the increase of Diva's apoptotic activity. Thus, these results indicate the existence of a previously undiscovered mechanism by which NM23-H2 involves in the regulation of Diva-mediated apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Cell Line
  • Down-Regulation
  • Feedback / physiology
  • Gene Expression Regulation / physiology
  • HeLa Cells
  • Humans
  • Kidney / cytology*
  • Kidney / metabolism*
  • NM23 Nucleoside Diphosphate Kinases
  • Nucleoside-Diphosphate Kinase / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Signal Transduction / physiology*

Substances

  • BCL2-like 10 protein
  • NM23 Nucleoside Diphosphate Kinases
  • Proto-Oncogene Proteins c-bcl-2
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase