FANCI is a negative regulator of Akt activation.

Akt is a critical mediator of the oncogenic PI3K pathway, and its activation is regulated by kinases and phosphatases acting in opposition. We report here the existence of a novel protein complex that is composed minimally of Akt, PHLPP1, PHLPP2, FANCI, FANCD2, USP1 and UAF1. Our studies show that depletion ...
of FANCI, but not FANCD2 or USP1, results in increased phosphorylation and activation of Akt. This activation is due to a reduction in the interaction between PHLPP1 and Akt in the absence of FANCI. In response to DNA damage or growth factor treatment, the interactions between Akt, PHLPP1 and FANCI are reduced consistent with the known phosphorylation of Akt in response to these stimuli. Furthermore, depletion of FANCI results in reduced apoptosis after DNA damage in accord with its role as a negative regular of Akt. Our findings describe an unexpected function for FANCI in the regulation of Akt and define a previously unrecognized intersection between the PI3K-Akt and FA pathways.
Mesh Terms:
Apoptosis, Cell Line, Tumor, Enzyme Activation, Fanconi Anemia, Fanconi Anemia Complementation Group D2 Protein, Gene Deletion, Humans, Multiprotein Complexes, Nuclear Proteins, Phosphoprotein Phosphatases, Phosphorylation, Protein Binding, Proto-Oncogene Proteins c-akt, RNA, Small Interfering
Cell Cycle
Date: Apr. 21, 2016
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