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Unformatted text preview: are inhibited by interactions with the antiapoptotic
family members, such as Bcl-2. The BH3-only family members are upstream
members of the cascade, regulated by the signals that induce cell death
(e.g., DNA damage) or cell survival (e.g., growth factors). When activated,
the BH3-only family members antagonize the antiapoptotic Bcl-2 family
members, activating the multidomain proapoptotic proteins and tipping
the balance in favor of caspase activation and cell death. Antiapoptotic Bcl-2
Bim BH4 BH3 BH1 BH2 BH3 BH1 BH2 FIGURE 17.6 BH3 The Bcl-2 family The Bcl-2 family of
proteins is divided into three functional groups. Antiapoptotic proteins (e.g., Bcl-2 and Bcl-xL) have four Bcl-2
homology domains (BH1–BH4). The multidomain
proapoptotic proteins (e.g., Bax and Bak) have three
homology domains (BH1–BH3), whereas the BH3-only
proapoptotic proteins (e.g., Bid, Bad, Noxa, Puma, and
Bim) have only one homology domain (BH3). This material...
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