Genetics of Apoptosis

later, expression of Bax was shown to be capable of directly triggering apoptosis (Xiang
et al., 1996). Since the discovery of Bcl-2 and Bax, the BH family in mammalian cells
has expanded by 18 members, with six acting principally as survival factors, and 12
hastening cell death in various experimental systems (Antonsson and Martinou, 2000)
(Table 1). Further clouding our understanding of these fundamentally opposed
activities are the rare observations of a BH protein changing its stripes. For example,
introduction of proapoptotic Bax into embryonic neurons promoted survival in the
absence of neurotrophic factors (Middleton et al., 1996). In some cases, too much
survival protein is a bad thing, resulting in apoptotic death. Homologs of BH proteins
exist in all metazoans and several animal DNA viruses (Barry and McFadden, 1998;
Wiens et al., 2000). C.elegans has both a cell-survival and a death-promoting homolog
(Liu and Hengartner, 1999), while only proapoptotic versions have been identified
to date in D.melanogaster (Vernooy et al., 2000).

2.1

Rheostat model of dimerization

Early experiments showed that the relative steady-state levels of antiapoptotic BH
members and death-promoting BH members correlated with the cellular sensitivity
to a death stimulus, such as withdrawal of growth factors (Oltvai et al., 1993).
Moreover, the relative amounts of pro- and antiapoptotic members were manifested
by differential associations between these factors (Oltvai and Korsmeyer, 1994). In

Table 1. Chronology of Bcl-2 homology family

50 GENETICS OF APOPTOSIS