mTORC1 alters the expression of glycolytic genes by regulating KPNA2 abundances.

Mammalian target of rapamycin complex 1 (mTORC1) plays important roles in regulating cell growth and proliferation, and the aberrant activation of mTORC1 has been observed in many human diseases. However, the proteins regulated by mTORC1 activation and their roles in mTORC1 downstream functions are still poorly understood. Using proteomic analysis, we found that proteins regulated by mTORC1 in MEFs could be categorized into eight functional groups including protein nuclear import and glycolysis. The positive regulation of Karyopherin subunit alpha-2 (KPNA2), an importer protein involved in protein nuclear import, by mTORC1 was verified in several other mouse and human cell lines. The regulation occurred at the transcriptional level, rather than at the level of S6K1- and 4E-BP1-dependent protein synthesis. KPNA2 knockdown partially blocked upregulation of glycolytic genes by mTORC1 activation, indicating that mTORC1 activation enhanced expression of glycolytic genes by increasing KPNA2 abundances. Furthermore, KPNA2 knockdown had no effects on the expression and subcellular localization of HIF1α, a transcription factor involved in regulating glycolytic genes downstream of mTORC1. In conclusion, our results proved that KPNA2 regulated the expression of glycolytic genes downstream of mTORC1 in a HIF1α-independent manner.

Pubmed ID: 26844761 RIS Download