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Some Clues as to the Regulation, Expression, Function, and Distribution of Fructosamine‐3‐Kinase and Fructosamine‐3‐Kinase‐Related Protein
Author(s) -
CONNER JAMES R.,
BEISSWENGER PAUL J.,
SZWERGOLD BENJAMIN S.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1333.095
Subject(s) - gene knockdown , fructosamine , biology , kinase , microbiology and biotechnology , chemistry , gene , biochemistry , diabetes mellitus , endocrinology
A bstract : Fructosamine‐3‐kinase (FN3K) and the more recently discovered fructosamine‐3‐kinase‐related protein (FN3KRP) appear to protect proteins from nonenzymatic glycation. To gain a better understanding of these enzymes we performed a series of investigations including (1) in silico comparisons of their promoters; (2) real‐time PCR analysis of their expression in human tissues; (3) effects of hyperglycemia, interleukin‐1β (IL‐1β), and nuclear factor kappa‐B (NFκB) activation on their mRNA levels; (4) effects of small interfering RNA (siRNA) suppression of FN3K expression (knockdown) in cultured cells and (5) search of FN3K and FN3KRP homologs in available genomic and EST (expressed sequence tag) databases. Our results indicate that (1) both FN3K and FN3KRP promoters are TATA‐less and CAAT‐less and contain several homologous CpG islands and Sp1 binding sites. (2) Both genes are expressed in all human tissue examined, with FN3K showing significantly higher levels in tissues susceptible to nonenzymatic glycation and diabetic complications. (3) Treatment of fibroblasts with high glucose, IL‐1β, and activation of NFκB does not affect the expression of either FN3K or FN3KRP. (4) Knockdown of FN3K in cultured cells inhibits or arrests their growth. (5) FN3K‐like genes are widely distributed in nature, with the notable exception of insects and yeasts. These data suggest that FN3K and FN3KRP are constitutive “housekeeping” genes and that they play an important role in cell metabolism, possibly as deglycating enzymes.