Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1038/onc.2014.164 http://scihub22266oqcxt.onion/10.1038/onc.2014.164 C4172452!4172452!24931163     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Oncogene 2015 ; 34 (17): 2239-50 Nephropedia Template TP {{tp|p=24931163|t=2015. mTORC1 drives HIF-1? and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3 |pdf=|usr=}}{{24931163}} gab.com Text mTORC1 drives HIF-1 and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3 JO: Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=24931163 #FOAvip Recent clinical trials using rapalogues in tuberous sclerosis complex (TSC) show regression in volume of typically vascularised tumours including angiomyolipomas (AMLs) and sub-ependymal giant cell astrocytomas (SEGAs). By blocking mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signalling, rapalogue efficacy is likely to occur in part through suppression of hypoxia inducible factors (HIFs) and vascular endothelial growth factors (VEGFs). We show that rapamycin reduces HIF-1? protein levels, and to a lesser extent VEGF-A levels, in renal cystadenoma cells in a Tsc2+/? mouse model. We establish that mTORC1 drives HIF-1? protein accumulation through enhanced transcription of HIF-1? mRNA, a process that is blocked by either inhibition or knockdown of signal transducer and activation of transcription 3 (STAT3). Furthermore, we demonstrate that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1? mRNA transcription. mTORC1 also regulates HIF-1? synthesis on a translational level via co-operative regulation of both initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whilst HIF-1? degradation remains unaffected. We therefore propose that mTORC1 drives HIF-1? synthesis in a multi-faceted manner through 4E-BP1/eIF4E, S6K1 and STAT3. Interestingly, we observe a disconnect between HIF-1? protein levels and VEGF-A expression. While both S6K1 and 4E-BP1 regulate HIF-1? translation, VEGF-A is primarily under the control of 4E-BP1/eIF4E. S6K1 inhibition reduces HIF-1? but not VEGF-A expression, suggesting that mTORC1 mediates VEGF-A expression via both HIF-1?-dependent and -independent mechanisms. Our work has important implications for the treatment of vascularised tumours, where mTORC1 acts as a central mediator of STAT3, HIF-1?, VEGF-A and angiogenesis via multiple signalling mechanisms. Twit Text FOAVip mTORC1 drives HIF-1 and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3 ????Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=24931163 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24931163 #FOAvip English Wikipedia <ref>{{Cite pmid|24931163}}</ref> mTORC1 drives HIF-1? and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3 #MMPMID24931163 Dodd KM; Yang J; Shen MH; Sampson JR; Tee AR Oncogene 2015[Apr]; 34 (17): 2239-50 PMID24931163show ga Recent clinical trials using rapalogues in tuberous sclerosis complex (TSC) show regression in volume of typically vascularised tumours including angiomyolipomas (AMLs) and sub-ependymal giant cell astrocytomas (SEGAs). By blocking mechanistic/mammalian target of rapamycin complex 1 (mTORC1) signalling, rapalogue efficacy is likely to occur in part through suppression of hypoxia inducible factors (HIFs) and vascular endothelial growth factors (VEGFs). We show that rapamycin reduces HIF-1? protein levels, and to a lesser extent VEGF-A levels, in renal cystadenoma cells in a Tsc2+/? mouse model. We establish that mTORC1 drives HIF-1? protein accumulation through enhanced transcription of HIF-1? mRNA, a process that is blocked by either inhibition or knockdown of signal transducer and activation of transcription 3 (STAT3). Furthermore, we demonstrate that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1? mRNA transcription. mTORC1 also regulates HIF-1? synthesis on a translational level via co-operative regulation of both initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whilst HIF-1? degradation remains unaffected. We therefore propose that mTORC1 drives HIF-1? synthesis in a multi-faceted manner through 4E-BP1/eIF4E, S6K1 and STAT3. Interestingly, we observe a disconnect between HIF-1? protein levels and VEGF-A expression. While both S6K1 and 4E-BP1 regulate HIF-1? translation, VEGF-A is primarily under the control of 4E-BP1/eIF4E. S6K1 inhibition reduces HIF-1? but not VEGF-A expression, suggesting that mTORC1 mediates VEGF-A expression via both HIF-1?-dependent and -independent mechanisms. Our work has important implications for the treatment of vascularised tumours, where mTORC1 acts as a central mediator of STAT3, HIF-1?, VEGF-A and angiogenesis via multiple signalling mechanisms. ämTORC1 drives HIF-1? and VEGF-A signalling via multiple mechanisms inv(epmc).pdf DeepDyve Pubget Overpricing