Circadian Regulation of mTOR by the Ubiquitin Pathway in Renal Cell Carcinoma

摘要: Circadian clock systems regulate many biologic functions, including cell division and hormone secretion in mammals. In this study, we explored the effects of circadian control on pivot growth regulatory mTOR, activity which is deregulated tumor cells compared with normal cells. Specifically, investigated whether antitumor effect an mTOR inhibitor could be improved by changing its dosing schedule RenCa tumor-bearing mice. Active, phosphorylated displayed a 24-hour rhythm, levels total protein (but not mRNA) also showed rhythm masses. Through investigations oscillation mechanism for expression, identified ubiquitination factor Fbxw7 as regulator that oscillated expression manner opposite from mTOR. transcription was regulated D-site-binding protein. Notably, administration everolimus during periods elevated survival Our findings demonstrate systems, influence inhibitors.