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Unformatted text preview: 14-3-3 proteins, which sequester FOXO in an inactive form in the
cytoplasm (see Figure 15.32). In the absence of growth factor signaling and
Akt activity, FOXO is released from 14-3-3 and translocates to the nucleus,
stimulating transcription of proapoptotic genes, including the gene encoding the BH3-only protein, Bim. Akt and its downstream target GSK-3 also
regulate other transcription factors with roles in cell survival, including p53
and NF-kB, which control the expression of additional Bcl-2 family members. In addition, the level of the antiapoptotic Bcl-2 family member Mcl-1
may be modulated via translational regulation by both GSK-3 and the
mTOR pathway (see Figure 15.33). These multiple effects on members of
the Bcl-2 family converge to regulate the intrinsic pathway of apoptosis, PUMA
Noxa Apoptosis FIGURE 17.10 Role of p53 in DNA damage-induced apoptosis DNA damage leads to activation of the ATM and Chk2 protein kinases, which phosphorylate
and stabilize p53 resulting in rapid increases in p53 levels. The protein p53 then
activates transcription of genes encodin...
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