Nuclear partners of Bcl-2: Bax and PML.
A milestone in understanding the functioning of the antiapoptotic cytoplasmic protein Bcl-2 was the discovery that Bcl-2 was capable of heterodimerising with the pro-apoptotic protein Bax at the mitochondrial level, creating a delicate balance of cell death preventing and promoting regulators. In recent years we identified substantial pools of Bcl-2 and Bax in nucleoplasm as well. We demonstrated that nuclear Bcl-2 controls cellular proliferation and, in an indirect manner, apoptosis. Sound support for functional presence of nuclear Bcl-2 and Bax would be evidence of Bcl-2-Bax binding in this compartment. Here we show by immunoprecipitation-using a battery of commercially available, monoclonal antibodies-that Bcl-2 binds Bax in nuclei of human breast cancer cells. Interestingly, findings by others pointed at an interaction between the product of the promyelocytic leukemia gene, the PML protein, and Bax. PML plays a part in cell proliferation and apoptosis, a rather similar role we assigned to nuclear Bcl-2. Nuclear Bcl-2, but not Bax, was found to immunoprecipitate with nuclear PML. These data show that binding of Bcl-2 with structurally and functionally related proteins extends to the nucleus, emphasizing its pivotal role in Bcl-2-mediated actions.
Hoetelmans
R W M
RW
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands. Hoetelmans@hotmail.com
D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D000071156:Promyelocytic Leukemia Protein; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein
D000911:Antibodies, Monoclonal; C494826:BAX protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; C070576:PML protein, human