Nuclear partners of Bcl-2: Bax and PML

DNA and Cell Biology
R W M Hoetelmans

Abstract

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 B...Continue Reading

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Citations

Mar 12, 2013·Cellular and Molecular Life Sciences : CMLS·Liora LindenboimReuven Stein
Jun 7, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Hanna LewandowskaMarcin Kruszewski
Aug 5, 2015·International Journal of Oncology·Junwei WangFeifei She
Jun 7, 2007·Journal of Neuroscience Research·Diana M CittellyJ Regino Perez-Polo
Apr 4, 2018·Cell Cycle·Ruoyao Chen, Michael Overholtzer
Oct 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rasha H Al-SerwiNehal Elsherbiny

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