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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nature 2014 ; 513 (7518): 440-3 Nephropedia Template TP
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Coordinated regulation of protein synthesis and degradation by mTORC1 #MMPMID25043031
Nature 2014[Sep]; 513 (7518): 440-3 PMID25043031show ga
Eukaryotic cells coordinately control anabolic and catabolic processes to maintain cell and tissue homeostasis. The mechanistic target of rapamycin complex 1 (mTORC1) promotes nutrient-consuming anabolic processes, such as protein synthesis1. Here, we show that accompanying an increase in protein synthesis, mTORC1 activation also promotes an increased capacity for protein degradation. Cells with activated mTORC1 exhibited elevated levels of intact and active proteasomes through a global increase in the expression of genes encoding proteasome subunits. The increase in proteasome gene expression, cellular proteasome content, and rates of protein turnover downstream of mTORC1 were all dependent on induction of the transcription factor nuclear factor erythroid-derived 2-related factor 1 (NFE2L1 or NRF1). Genetic activation of mTORC1 through loss of the tuberous sclerosis complex tumor suppressors or physiological activation of mTORC1 in response to growth factors or feeding resulted in increased NRF1 expression in cells and tissues. We find that this NRF1-dependent elevation of proteasome levels serves to increase the intracellular pool of amino acids, which thereby influences rates of new protein synthesis. Therefore, mTORC1 signaling increases the efficiency of proteasome-mediated protein degradation for both quality control and as a mechanism to supply substrate for sustained protein synthesis.