Cooper5e_Ch17

Phosphorylation of foxo by akt creates a binding site

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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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This note was uploaded on 08/25/2009 for the course BIO 315 taught by Professor Steiner during the Spring '08 term at Kentucky.

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