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.