Biologists have found that the disorder of cellular energy can result in diseases related to aging. However, it’s been debated that how to maintain the order and stability of cellular energy while cells are affected under the diversity of environments. Thus, the cells can perform the well-functioned metabolism according to the theory above. The assistant professor, Lin Yu-Ti, of National Taiwan University and his cross-country research team has just published an innovative research project in the international science journal, Nature, on the genetic technology on February 9th, 2012. Their research contribution brings along a great hope for treating the syndromes of metabolism, cancers and the diseases related to aging.
Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms2, 3, 4, 5, 6, but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs7 remain enigmatic, and the substrate spectra of each KDAC lack comprehensive definition. Professor Lin Yu-Yi states that the breakthrough of this research project relies on the RNAi technique using RNA interference to clarify how cells maintain a normal metabolism by controlling the modification of protein acetylation for the adjustment to any environments in order to maintain the survival of cells and their clones.
The cross-country research team founded by National Taiwan University and the medical school of John Hopkins University have successfully developed their genetic technique of RNAi interference to explore the complexion and the functions of the regulation of protein acetylation in human cells. The research team constitutes a network of protein- acetylating in human cells and also have found many other functions of acetylation.
The research team found that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 and p300. Deacetylation of AMPK enhances physical interaction with the upstream kinase LKB1, leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. These findings provide new insights into previously underappreciated metabolic regulatory roles of HDAC1 in coordinating nutrient availability and cellular responses upstream of AMPK, and demonstrate the importance of high-throughput genetic interaction profiling to elucidate functional specificity and critical substrates of individual human KDACs potentially valuable for therapeutic applications.
Yang Pan-Chyr, the superintendent of NTU medical school recognized that this medical research will definitely be a great help to solve and to treat many severe diseases in addition to its profound achievement in Taiwan’s medical history. Meanwhile, this also shows the outstanding academic performance of the young scholars from Taiwan, which just made them competitive to the international research center of medical areas.
This top research project is well supported by NRPB (National Research Program for Biopharmaceuticals), National Science Council, the Aim for the Top University Project founded by the Ministry of Education, National Health Research Institute, Taiwan Liver Research Foundation, and the National Platform of RNAi interference.
This research paper has just been published in the latest scientific journal, Nature, on February 9th, 2012 by the assistant professor, Lin Yi-Yu, and his research team members of NTU medical school. Other corporative authors are Dr. Jef Boeke, Joel Bader, Rafael Irizarry of the medical school of John Hopkins University, Dr. Lu Jin-Ying of NTU Hospital and Dr. Lin Chih-Lung of the National Platfor, of RNAi interference.