کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6494133 | 1418334 | 2018 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells
ترجمه فارسی عنوان
تنظیم مقدمه ای از متابولیسم در سلول های سرطانی با کمبود هورمون های فسفره هیدراتاز
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کلمات کلیدی
متابولیسم، سرطان، فسفر پروتئومیکس، مدل سازی،
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
چکیده انگلیسی
Deregulated signal transduction and energy metabolism are hallmarks of cancer and both play a fundamental role in tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes. We identified previously reported functionally relevant phosphosites and potentially novel regulatory residues in enzymes of the central carbon metabolism. In particular, we showed that pyruvate dehydrogenase (PDHA1) enzymatic activity is inhibited by increased phosphorylation in FH-deficient cells, restricting carbon entry from glucose to the tricarboxylic acid cycle. Moreover, we confirmed PDHA1 phosphorylation in human FH-deficient tumours. Our work provides a novel approach to investigate how post-translational modifications of enzymes regulate metabolism and could have important implications for understanding the metabolic transformation of FH-deficient cancers with potential clinical applications.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Metabolic Engineering - Volume 45, January 2018, Pages 149-157
Journal: Metabolic Engineering - Volume 45, January 2018, Pages 149-157
نویسندگان
Emanuel Gonçalves, Marco Sciacovelli, Ana S.H. Costa, Maxine Gia Binh Tran, Timothy Isaac Johnson, Daniel Machado, Christian Frezza, Julio Saez-Rodriguez,