mProX™ Human RPS6KB1 Stable Cell Line

Xia, Li. et al. "Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer." Autophagy, 2023.
The MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) plays a crucial role in facilitating cell growth and is often activated in cancer. The activation of MTORC1 requires the translocation of the complex from the cytosol to the lysosomal surface, which is governed by the RRAG GTPases. In this study, it was demonstrated that the transcription factors MEF2A and MEF2D work together to regulate MTORC1 activation by controlling its movement between the cytosol and lysosome. This was achieved through their regulation of the transcription of FNIP1 and FNIP2, components of the FLCN-FNIP1 or FNIP2 complex which aids in the recruitment and activation of MTORC1. Additionally, it was discovered that the protein kinase SRC/c-Src directly phosphorylates MEF2D at three tyrosine residues, enhancing its transcriptional activity and promoting MTORC1 activation. This phosphorylation was found to be elevated in human pancreatic cancers, correlating with increased MTORC1 activity. Depletion of MEF2A and MEF2D, or expression of a mutant MEF2D unable to be phosphorylated, was shown to suppress tumor cell growth. These findings elucidate a novel transcriptional regulatory mechanism of MTORC1 involved in cell anabolism and proliferation, highlighting its crucial role in pancreatic cancer progression.
Xia, Li. et al. "Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer." Autophagy, 2023.
Pubmed: 37772772   DOI: 10.1080/15548627.2023.2259735

Raza, Sana. et al. "Fructose-induced perturbation in cellular proteostasis via RPS6KB1 promotes hepatic steatosis." Biochimica et biophysica acta. Molecular cell research, 2023.
This study examines the role of dietary fructose intake in the development of non-alcoholic fatty liver disease (NAFLD), specifically through its impact on hepatic de novo lipogenesis (DNL). Using HepG2 cells, the researchers discovered that DNL induced by fructose involves the ribosomal protein S6 kinase B1 (RPS6KB1), which stimulates hepatic protein synthesis and leads to endoplasmic reticulum (ER)-stress and subsequent expression of pro-lipogenic genes. Inhibiting protein synthesis through cycloheximide or an RPS6KB1 inhibitor decreased ER-stress and expression of fatty acid synthase (FASN). This was further supported by the analysis of human NAFLD transcriptomic datasets, which showed an increase in protein synthesis pathways in patients with hepatic steatosis. These findings suggest that targeting RPS6KB1 may be a potential therapeutic strategy for managing fructose-induced hepatic steatosis in NAFLD.
Raza, Sana. et al. "Fructose-induced perturbation in cellular proteostasis via RPS6KB1 promotes hepatic steatosis." Biochimica et biophysica acta. Molecular cell research, 2023.
Pubmed: 37741573   DOI: 10.1016/j.bbamcr.2023.119597