They are inhibited by interactions with the

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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 Bcl-xL Proapoptotic multidomain Bax Bak Proapoptotic BH3-only Bid Bad Noxa Puma 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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