TMBIM protein family: ancestral regulators of cell death

Oncogene. 2015 Jan 15;34(3):269-80. doi: 10.1038/onc.2014.6. Epub 2014 Feb 24.


The control of apoptosis in mammals has been historically associated with the activity of the BCL-2 family of proteins at the mitochondria. In the past years, a novel group of cell death regulators have emerged, known as the Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) protein family. This group of proteins is composed of at least six highly conserved members expressed in mammals, with homologs in insects, fish, plants, viruses and yeast. Different studies indicate that all TMBIM family members have inhibitory activities in different setting of apoptosis. Here, we overview and integrate possible mechanisms underlying the impact of the TMBIM protein family in the regulation of cell death, which include activities at diverse subcellular compartments, including death receptor regulation, modulation of endoplasmic reticulum (ER) calcium homeostasis, ER stress signaling, autophagy, reactive oxygen species production, among other effects. The possible intersection between the BCL-2 and TMBIM family in the control of cell death is also discussed, in addition to their implication in the progression of cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Endoplasmic Reticulum Stress / genetics
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Models, Genetic
  • Multigene Family*
  • Neoplasms / genetics
  • Signal Transduction / genetics


  • Apoptosis Regulatory Proteins
  • Membrane Proteins