CYTOSOL-TO-MEMBRANE REDISTRIBUTION OF BAX AND BCL-X-L DURING APOPTOSIS

Bcl-2, Bcl-X-L, and fax are members of the Bcl-2 family that play key roles in the regulation of apoptosis. These proteins are believed to b e membrane bound and their ability to undergo both homodimerization an d heterodimerization has been proposed to regulate apoptosis. Herein w e report that in murine thymocytes, Bcl-2 is exclusively membrane-boun d, whereas Bar is present predominantly in the cytosol and Bcl-X-L is present in both soluble and membrane-bound forms. Induction of apoptos is in murine thymocytes by dexamethasone or gamma-irradiation shifts t he subcellular locations of Bar and Bcl-X-L from soluble to membrane-b ound forms. A similar shift in the localization of Bar from the cytoso l to membranes was observed in HL-60 leukemia cells upon induction of apoptosis by staurosporine. Inhibition of apoptosis with cycloheximide inhibits the movement of Bar and Bcl-X-L in thymocytes from the cytos ol into membranes induced by dexamethasone treatment. These movements may represent an important step in the pathway by which members of thi s family regulate apoptosis.