(664.6) The RNA Binding Protein AUF1 Regulates Phosphorylation of The mTORC2 Target Akt

Poster Board Number: A273

Aparna Ragupathi (Rutgers Biomedical Health Sciences - Robert Wood Johnson Medical School), Mei-ling Li (Rutgers Biomedical Health Sciences - Robert Wood Johnson Medical School), Nikhil Patel (Rutgers Biomedical Health Sciences - Robert Wood Johnson Medical School), Guy Werlen (Rutgers Biomedical Health Sciences - Robert Wood Johnson Medical School), Gary Brewer (Rutgers Biomedical Health Sciences - Robert Wood Johnson Medical School), Estela Jacinto (Rutgers Biomedical Health Sciences - Robert Wood Johnson Medical School)

mTOR, which is part of mTOR complex 1 (mTORC1) and mTORC2, controls cellular metabolism in response to levels of nutrients and other growth signals. A hallmark of mTORC2 activation is the phosphorylation of Akt, which becomes upregulated in cancer.  How mTORC2 modulates Akt phosphorylation remains poorly understood. Here, we found that the RNA binding protein, AUF1 (ARE/poly(U)-binding/degradation factor 1), modulates mTORC2/Akt signaling.  AUF1 is required for Akt phosphorylation.  It also mediates phosphorylation of the mTORC2-modulated metabolic enzyme GFAT1 at Ser243. Reciprocally, mTORC2 could also modulate AUF1.  Conditions that enhance mTORC2 signaling, such as serum restimulation or acute glutamine withdrawal augments AUF1 phosphorylation while mTOR inhibition abolishes AUF1 phosphorylation.  Our findings unravel a role for AUF1 in mTORC2/Akt signaling.  Targeting AUF1 could serve as a novel treatment strategy for cancers with upregulated mTORC2/Akt signaling.

Support or Funding Information

The authors gratefully acknowledge funding from NIH (GM-137493).