Our hosting provider is experiencing network issues which may result in intermittent downtime. We apologize for any inconveniences this may cause.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum.

Proapoptotic BCL-2 family members BAX and BAK are required for the initiation of mitochondrial dysfunction during apoptosis and for maintaining the endoplasmic reticulum (ER) Ca(2+) stores necessary for Ca(2+)-dependent cell death. Conversely, antiapoptotic BCL-2 has been shown to decrease Ca(2+) concentration in the ER. We found that Bax(-/-)Bak(-/-) double-knockout (DKO) cells have reduced resting ER Ca(2+) levels because of increased Ca(2+) leak and an increase in the Ca(2+)-permeable, hyperphosphorylated state of the inositol trisphosphate receptor type 1 (IP3R-1). The ER Ca(2+) defect of DKO cells is rescued by RNA interference reduction of IP3R-1, supporting the argument that this channel regulates the increased Ca(2+) leak in these cells. BCL-2 and IP3R-1 physically interact at the ER, and their binding is increased in the absence of BAX and BAK. Moreover, knocking down BCL-2 decreases IP3R-1 phosphorylation and ER Ca(2+) leak rate in the DKO cells. These findings support a model in which BCL-2 family members regulate IP3R-1 phosphorylation to control the rate of ER Ca(2+) leak from intracellular stores.

Pubmed ID: 15613488


  • Oakes SA
  • Scorrano L
  • Opferman JT
  • Bassik MC
  • Nishino M
  • Pozzan T
  • Korsmeyer SJ


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

January 4, 2005

Associated Grants

  • Agency: NIAID NIH HHS, Id: K08 AI 054650
  • Agency: NCI NIH HHS, Id: R37 CA 50239
  • Agency: Telethon, Id: TCP02016

Mesh Terms

  • Animals
  • Apoptosis
  • Calcium
  • Calcium Channels
  • Calcium-Transporting ATPases
  • Endoplasmic Reticulum
  • Inositol 1,4,5-Trisphosphate Receptors
  • Membrane Proteins
  • Mice
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Cytoplasmic and Nuclear
  • Thapsigargin
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein