Programmed cell death (apoptosis) is controlled in part by the Bcl-2 family of apoptosis-promoting (Bak, Bax, Bid) and apoptosis-inhibiting (Bcl-2, Bcl-xL) proteins. Beginning on page 903, Griffiths et al. examine what may be one of the earliest events in apoptosis: the effects of damage signals on the pro-apoptotic protein Bak. Using flow cytometry, they show that although the amount of Bak does not change early on, an epitope at Bak's NH2 terminus becomes accessible after various apoptosis-inducing events, DNA strand breaks and changes in protein phosphorylation and transcription, are induced by etoposide, staurosporine, or dexamethasone. However, the epitope is not exposed by activation of the Fas-dependent apoptotic pathway.
In untreated cells, Bcl-xL and Bak coimmunoprecipitate and immunofluorescence data reveal a close association between the two proteins and mitochondria. Dissociation of Bcl-xL from Bak, perhaps due to exposure of Bak's NH2 terminus, could account...
