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Danial, N.N., Gramm, C.F., Scorrano, L., Zhang, C-Y., Krauss, S., Ranger, A.M., Datta, S.R., Greenberg, M.E., Licklider, L.J., Lowell, B.B., Gygi, S.P. and Korsmeyer, S.J. (2003) BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature, 424, 952-956. doi:10.1038/nature01825

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• TITLE: Systematic analysis of diabetes- and glucose metabolism-related proteins and its application to Alzheimer’s disease

  AUTHORS: Jie Yang, Sen Li, Yan-Xin Liu

  KEYWORDS: Codon Biases; Protein-Protein Interaction Network; Transcription Factors; BAD Complex; Bioinformatics

  JOURNAL NAME: Journal of Biomedical Science and Engineering, Vol.6 No.6, June 26, 2013

  ABSTRACT: Alzheimer disease has been defined as Type 3 Diabetes due to their shared metabolic profiles. Like our previously research, results of Alzheimer’s disease and other neurodegenerative diseases, systematic analysis of diabetes- and glucose metabolism-related proteins also provides help in the treatment of Alzheimer’s patients. Some interesting results indicate that diabetes-related proteins (DRPs) are rich in Lys and the content of Trp can distinguish between type 1 and type 2 diabetes mellitus in particular, while glucose metabolism-related proteins (GMRPs) possess Leurich and Trp-poor character. Moreover, the usage biases of codons depend on GC contents to a great extent, in concord with all codons of the highly expressed genes with the terminal of C/G. Especially, the deficit of CpG dinucleotides is largely attributed to the hypermutability of methylated CpGs to UpGs by the mutational pressure. Besides a common node insulin receptor, there are some similar node proteins, such as glucose transporter member, protein tyrosine phosphatase, and adipose metabolism signal protein. The sharing proteins involve glucagon, amylin, insulin, PPARγ, angiopoietin, PC-1/ENPP1, and adiponectin mediated signal pathway. Meanwhile, the gene sequences of node proteins contained the binding sites of 37 transcription factors divide into four kinds of superclasses. Additionally, BAD complex can integrate pathways of glucose metabolism and apoptosis by BH3 domain of BAD directly interacting with GK as well as GK binding with the consensus motif [G]-[1]-[K]-[2]-[S/T] or [L/M]-[R/K]-[2]-[T] of PP1 or WAVE1. This facilitates the therapies for diabetes mellitus as well as Alzheimer’s disease.