Sequestration of BAD protein by 14-3-3

Stable Identifier
R-HSA-139899
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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14-3-3 proteins bind BAD phosphorylated by activated AKT on serine residue S99 (corresponds to mouse Bad serine residue S136). Binding of 14-3-3 proteins to p-S99-BAD facilitates subsequent phosphorylation of BAD on serine residue S118 (corresponds to mouse serine S155), which disrupts binding of BAD to BCL2 proteins and promotes cell survival (Datta et al. 2000). Caspase-3 mediated cleavage of 14-3-3 proteins releases BAD and promotes apoptosis (Won et al. 2003). All known 14-3-3 protein isoforms (beta/alpha i.e. YWHAB, gamma i.e. YWHAG, zeta/delta i.e. YWHAZ, epsilon i.e. YWHAE, eta i.e. YWHAH, sigma i.e. SFN and theta i.e. YWHAQ) can interact with BAD and inhibit it (Subramanian et al. 2001, Chen et al. 2005).

Literature References
PubMed ID Title Journal Year
15660102 Association of 14-3-3gamma and phosphorylated bad attenuates injury in ischemic astrocytes

Chen, XQ, Fung, YW, Yu, AC

J. Cereb. Blood Flow Metab. 2005
11697890 Functional conservation of 14-3-3 isoforms in inhibiting bad-induced apoptosis

Subramanian, RR, Masters, SC, Zhang, H, Fu, H

Exp. Cell Res. 2001
12657644 Cleavage of 14-3-3 protein by caspase-3 facilitates bad interaction with Bcl-x(L) during apoptosis

Won, J, Kim, DY, La, M, Kim, D, Meadows, GG, Joe, CO

J Biol Chem 2003
10949026 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation

Datta, SR, Katsov, A, Hu, L, Petros, A, Fesik, SW, Yaffe, MB, Greenberg, ME

Mol. Cell 2000
Participants
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Orthologous Events
Created