Apolipoprotein L2 contains a BH3-like domain but it does not behave as a BH3-only protein

Cell Death Dis. 2014 Jun 5;5(6):e1275. doi: 10.1038/cddis.2014.237.


Apolipoproteins of the L family are lipid-binding proteins whose function is largely unknown. Apolipoprotein L1 and apolipoprotein L6 have been recently described as novel pro-death BH3-only proteins that are also capable of regulating autophagy. In an in-silico screening to discover novel putative BH3-only proteins, we identified yet another member of the apolipoprotein L family, apolipoprotein L2 (ApoL2), as a BH3 motif-containing protein. ApoL2 has been suggested to behave as a BH3-only protein and mediate cell death induced by interferon-gamma or viral infection. As previously described, we observed that ApoL2 protein was induced by interferon-gamma. However, knocking down its expression in HeLa cells did not regulate cell death induced by interferon-gamma. Overexpression of ApoL2 did not induce cell death on its own. ApoL2 did not sensitize or protect cells from overexpression of the BH3-only proteins Bmf or Noxa. Furthermore, siRNA against ApoL2 did not alter sensitivity to a variety of death stimuli. We could, however, detect a weak interaction between ApoL2 and Bcl-2 by immunoprecipitation of the former, suggesting a role of ApoL2 in a Bcl-2-regulated process like autophagy. However, in contrast to what has been described about its homologs ApoL1 and ApoL6, ApoL2 did not regulate autophagy. Thus, the role, if any, of ApoL2 in cell death remains to be clarified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apolipoproteins / genetics
  • Apolipoproteins / metabolism*
  • Apolipoproteins L
  • Cell Death / physiology
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Lipoproteins, HDL / genetics
  • Lipoproteins, HDL / metabolism*
  • Mitochondrial Membrane Transport Proteins
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*


  • APOL2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Apolipoproteins
  • Apolipoproteins L
  • BMF protein, human
  • IFNG protein, human
  • Lipoproteins, HDL
  • Mitochondrial Membrane Transport Proteins
  • PMAIP1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RTL10 protein, human
  • Interferon-gamma