title: The ability of Bcl-x(L) and Bcl-2 to prevent apoptosis can be differentially regulated.
abstract: Although expression of Bcl-2 has been shown to prevent apoptosis under many circumstances, there are several systems in which Bcl-2 fails to promote cell survival. We have previously reported that Bcl-2 and Bcl-x(L) display differential ability to protect WEHI-231 cells from multiple inducers of apoptosis. A possible explanation for this paradox was provided by the discovery of Bax. Bax is a Bcl-2-related protein which can inhibit the ability of Bcl-2 to enhance the survival of growth factor-dependent cell lines in the absence of growth factor. Consistent with the possibility that Bcl-2 function in WEHI-231 cells is inhibited by Bax, WEHI-231 cells were found to express a high level of Bax. To directly test the effects of Bax expression on Bcl-x(L) function, FL5.12 cells were transfected with both genes. Although Bax overexpression can inhibit Bcl-2 from prolonging cell survival upon growth factor withdrawal, Bax overexpression did not inhibit Bcl-x(L) from preventing apoptosis in this cell line. Although Bcl-2 and Bcl-x(L) were both found to be able to form heterodimers with Bax, the majority of Bax in both cases was not complexed to a partner. Our data suggest that Bcl-x(L) does not function by simply preventing the formation of Bax homodimers which promote cell death. Instead Bax appears to display selectivity in its ability to inhibit Bcl-2 but not Bcl-x(L) from prolonging survival. Furthermore, our data suggest that the abilities of Bcl-2 and Bcl-x(L) to promote cell survival are not identical and can be independently regulated within a cell. Regulation of a cell's apoptotic threshold is likely to result from a complex set of interactions among Bcl-2 family members and other, as yet uncharacterised, regulators of apoptosis.
authors.affiliation: Department of Pathology and Cancer Research Center, University of Chicago.
authors.forename: A R
authors.initials: AR
authors.lastname: Gottschalk
authors.forename: L H
authors.initials: LH
authors.lastname: Boise
authors.forename: Z N
authors.initials: ZN
authors.lastname: Oltvai
authors.forename: M A
authors.initials: MA
authors.lastname: Accavitti
authors.forename: S J
authors.initials: SJ
authors.lastname: Korsmeyer
authors.forename: J
authors.initials: J
authors.lastname: Quintáns
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson