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10.1186/s12943-017-0626-7 http://scihub22266oqcxt.onion/10.1186/s12943-017-0626-7 C5341177!5341177!28270148     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Mol+Cancer 2017 ; 16 (ä): ä Nephropedia Template TP {{tp|p=28270148|t=2017. MDM4 actively restrains cytoplasmic mTORC1 by sensing nutrient availability |pdf=|usr=}}{{28270148}} gab.com Text MDM4 actively restrains cytoplasmic mTORC1 by sensing nutrient availability JO: Mol Cancer http://www.kidney.de/pget.php?&tw=1&pmid=28270148 #FOAvip Background: Many tumor-related factors have shown the ability to affect metabolic pathways by paving the way for cancer-specific metabolic features. Here, we investigate the regulation of mTORC1 by MDM4, a p53-inhibitor with oncogenic or anti-survival activities depending on cell growth conditions. Method: MDM4-mTOR relationship was analysed through experiments of overexpression or silencing of endogenous proteins in cell culture and using purified proteins in vitro. Data were further confirmed in vivo using a transgenic mouse model overexpressing MDM4. Additionally, the Cancer Genome Atlas (TCGA) database (N?=?356) was adopted to analyze the correlation between MDM4 and mTOR levels and 3D cultures were used to analyse the p53-independent activity of MDM4. Results: Following nutrient deprivation, MDM4 impairs mTORC1 activity by binding and inhibiting the kinase mTOR, and contributing to maintain the cytosolic inactive pool of mTORC1. This function is independent of p53. Inhibition of mTORC1 by MDM4 results in reduced phosphorylation of the mTOR downstream target p70S6K1 both in vitro and in vivo in a MDM4-transgenic mouse. Consistently, MDM4 reduces cell size and proliferation, two features controlled by p70S6K1, and, importantly, inhibits mTORC1-mediated mammosphere formation. Noteworthy, MDM4 transcript levels are significantly reduced in breast tumors characterized by high mTOR levels. Conclusion: Overall, these data identify MDM4 as a nutrient-sensor able to inhibit mTORC1 and highlight its metabolism-related tumor-suppressing function. Electronic supplementary material: The online version of this article (doi:10.1186/s12943-017-0626-7) contains supplementary material, which is available to authorized users. Twit Text FOAVip MDM4 actively restrains cytoplasmic mTORC1 by sensing nutrient availability ????Mol Cancer http://www.kidney.de/pget.php?&tw=1&pmid=28270148 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28270148 #FOAvip English Wikipedia <ref>{{Cite pmid|28270148}}</ref> MDM4 actively restrains cytoplasmic mTORC1 by sensing nutrient availability #MMPMID28270148 Mancini F; Teveroni E; Di Conza G; Monteleone V; Arisi I; Pellegrino M; Buttarelli M; Pieroni L; D?Onofrio M; Urbani A; Pontecorvi A; Mazzone M; Moretti F Mol Cancer 2017[]; 16 (ä): ä PMID28270148show ga Background: Many tumor-related factors have shown the ability to affect metabolic pathways by paving the way for cancer-specific metabolic features. Here, we investigate the regulation of mTORC1 by MDM4, a p53-inhibitor with oncogenic or anti-survival activities depending on cell growth conditions. Method: MDM4-mTOR relationship was analysed through experiments of overexpression or silencing of endogenous proteins in cell culture and using purified proteins in vitro. Data were further confirmed in vivo using a transgenic mouse model overexpressing MDM4. Additionally, the Cancer Genome Atlas (TCGA) database (N?=?356) was adopted to analyze the correlation between MDM4 and mTOR levels and 3D cultures were used to analyse the p53-independent activity of MDM4. Results: Following nutrient deprivation, MDM4 impairs mTORC1 activity by binding and inhibiting the kinase mTOR, and contributing to maintain the cytosolic inactive pool of mTORC1. This function is independent of p53. Inhibition of mTORC1 by MDM4 results in reduced phosphorylation of the mTOR downstream target p70S6K1 both in vitro and in vivo in a MDM4-transgenic mouse. Consistently, MDM4 reduces cell size and proliferation, two features controlled by p70S6K1, and, importantly, inhibits mTORC1-mediated mammosphere formation. Noteworthy, MDM4 transcript levels are significantly reduced in breast tumors characterized by high mTOR levels. Conclusion: Overall, these data identify MDM4 as a nutrient-sensor able to inhibit mTORC1 and highlight its metabolism-related tumor-suppressing function. Electronic supplementary material: The online version of this article (doi:10.1186/s12943-017-0626-7) contains supplementary material, which is available to authorized users. äMDM4 actively restrains cytoplasmic mTORC1 by sensing nutrient availab(epmc).pdf DeepDyve Pubget Overpricing