Protein Acetylation at the Interface of Genetics, Epigenetics and Environment in Cancer

Metabolites

Mio Harachi¹  Noriyuki Shibata¹  Kenta Masui¹  PaulS. Mischel²  WebsterK. Cavenee³ 

[1] Department of Pathology, Division of Pathological Neuroscience, Tokyo Women’s Medical University, Tokyo 162-8666, Japan;Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA;Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA;

关键词: metabolic reprogramming;    microenvironment;    protein acetylation;    epigenetics;    mechanistic target of rapamycin (mTOR) complexes;   

DOI  :  10.3390/metabo11040216

来源: DOAJ

【 摘 要 】

Metabolic reprogramming is an emerging hallmark of cancer and is driven by abnormalities of oncogenes and tumor suppressors. Accelerated metabolism causes cancer cell aggression through the dysregulation of rate-limiting metabolic enzymes as well as by facilitating the production of intermediary metabolites. However, the mechanisms by which a shift in the metabolic landscape reshapes the intracellular signaling to promote the survival of cancer cells remain to be clarified. Recent high-resolution mass spectrometry-based proteomic analyses have spotlighted that, unexpectedly, lysine residues of numerous cytosolic as well as nuclear proteins are acetylated and that this modification modulates protein activity, sublocalization and stability, with profound impact on cellular function. More importantly, cancer cells exploit acetylation as a post-translational protein for microenvironmental adaptation, nominating it as a means for dynamic modulation of the phenotypes of cancer cells at the interface between genetics and environments. The objectives of this review were to describe the functional implications of protein lysine acetylation in cancer biology by examining recent evidence that implicates oncogenic signaling as a strong driver of protein acetylation, which might be exploitable for novel therapeutic strategies against cancer.

【 授权许可】

Unknown