Proposed mechanism for MAP4K3 cell death signaling

Proposed mechanism for MAP4K3 cell death signaling. Activation of mTORC1 by MAP4K3 modulates the activity of eIF4B and eIF4E. Of these, eIF4E is a component of the CAP-binding complex eIF4F whereas eIF4B promotes the RNA helicase activity of eIF4A (reviewed in ref. ). eIF4F is a modulator of eukaryotic mRNA stability (). MAP4K3 signaling leads to up-regulation of the BH3-only proteins PUMA and BAD in an mTORC1-dependent manner. PUMA and BAD, in turn, are capable of neutralizing anti-apoptotic BCL-2 family members, leading to BAX activation and caspase-dependent cell death. In parallel, MAP4K3 signaling through JNK induces BIM phosphorylation. The direct activation of BAX by BIM, together with the neutralization of BCL-XL by PUMA or BAD, results in activation of the intrinsic apoptosis pathway.

Publication

MAP4K3 modulates cell death via the post-transcriptional regulation of BH3-only proteins. (2009) David Lam, et al. Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11978-11983. Figure: F5. Homo sapiens

Disease mentions