利用人類蛋白質體晶片探討ATP合成酶之交互作用蛋白

Revealing Novel Interacting Proteins of ATP Synthase by Human Proteome Microarray

蔡惠婷(Hui-Ting Tsai)

指導教授 ： 阮雪芬

國立臺灣大學/生命科學院/分子與細胞生物學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.10653

摘要

無資料

關鍵字

三磷酸腺苷合成酶β 次單位 ； 交互作用蛋白 ； 人類蛋白質體晶片 ； 有絲分裂原活化蛋白質激酶12

並列摘要

ATP synthase is essential for almost all organisms because ATP is the common “energy currency” of cells. It is a multimeric protein complex including beta subunit (ATP5B) that catalyzes the synthesis of ATP from ADP and phosphate. Although ATP synthase was initially thought to be located exclusively in the mitochondrial inner membrane, its presence has now been described on the outside of the plasma membrane of both normal cells (e.g. endothelial cells, hepatocytes and adipocytes) and tumor cells. We are interested to understand whether ATP5B interacts with different proteins and performs different functions. Here, we perform a human proteome microarray to reveal the novel interacting proteins with ATP5B and identified 16 proteins which interact strongly with ATP5B. The identified ATP5B interacting proteins are functionally enriched in mitogen activated protein kinase 12 (MAPK12) dependent pathways. Our previous results showed that ATP5B was overexpressed on the plasma membrane with the potential as a cell proliferation regulator in both breast and lung cancers. Hence we further combined ATP synthase inhibitor, citrovirodin, and MAPK12 inhibitor, and found this combination leads to addictive inhibition on lung cancer cell proliferation. Taken together, these findings suggest that these interacting proteins of ATP5B as a cell proliferation signal linking to MAPK12 in response to a variety of extracellular stimuli.

並列關鍵字

ATP synthase ； ATP5B ； interacting proteins ； human proteome microarray ； MAPK12

參考文獻

1. Pullman, M. E.; Penefsky, H. S.; Datta, A.; Racker, E., Partial resolution of the enzymes catalyzing oxidative phosphorylation. I. Purification and properties of soluble dinitrophenol-stimulated adenosine triphosphatase. J Biol Chem 1960, 235, 3322-9.

2. Boyer, P. D., The ATP synthase--a splendid molecular machine. Annu Rev Biochem 1997, 66, 717-49.

3. Hudson, G. S.; Mason, J. G.; Holton, T. A.; Koller, B.; Cox, G. B.; Whitfeld, P. R.; Bottomley, W., A gene cluster in the spinach and pea chloroplast genomes encoding one CF1 and three CF0 subunits of the H+-ATP synthase complex and the ribosomal protein S2. J Mol Biol 1987, 196, (2), 283-98.

4. Kanazawa, H.; Kayano, T.; Mabuchi, K.; Futai, M., Nucleotide sequence of the genes coding for alpha, beta and gamma subunits of the proton-translocating ATPase of Escherichia coli. Biochem Biophys Res Commun 1981, 103, (2), 604-12.

5. Walker, J. E.; Fearnley, I. M.; Gay, N. J.; Gibson, B. W.; Northrop, F. D.; Powell, S. J.; Runswick, M. J.; Saraste, M.; Tybulewicz, V. L., Primary structure and subunit stoichiometry of F1-ATPase from bovine mitochondria. J Mol Biol 1985, 184, (4), 677-701.