Bcl-2 and Bax proteins are present in interphase nuclei of mammalian cells

The Bcl-2 family of proteins comprises both cell death inhibiting and cell death promoting members, generally believed to be cytoplasmic and predomina ntly membrane-associated. Like Bcl-2, many Bcl-2-related proteins contain a C-terminal membrane insertion domain and much research is aimed at evaluat ing the functional role of their localization to the outer membranes of mit ochondria, the endoplasmic reticulum, and perinuclear membranes. However, c onfocal fluorescence microscopy of human breast cancer cells and rat colon cancer cells immunostained with commercial antibodies raised against differ ent epitopes of the anti-apoptotic Bcl-2 and the pro-apoptotic Bar protein revealed that these proteins are not only present in the cellular cytoplasm , but also within interphase nuclei, This was confirmed by Western blot ana lysis of isolated nuclei. In human cells, certain epitopes of Bcl-2, but no t of Bax, were also found to be associated with mitotic chromatin, Anti-est rogen treatment of human breast cancer cells or transfection with antisense bcl-2 led to a reduction in both cytoplasmic and nuclear Bcl-2, Transfecti on of human bcl-2 and bar into rat cells resulted in cytoplasmic and nuclea r Bcl-2 and Bax. This data seems in line with increasing evidence that the role of the Bcl-2 family of proteins should be extended to activities insid e the nuclear compartment.