Some clues as to the regulation, expression, function, and distribution of fructosamine-3-kinase and fructosamine-3-kinase-related protein.

Abstract:

: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-1beta (IL-1beta), and nuclear factor kappa-B (NFkappaB) 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-1beta, and activation of NFkappaB 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.

journal_name

Ann N Y Acad Sci

authors

Conner JR,Beisswenger PJ,Szwergold BS

doi

10.1196/annals.1333.095

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

824-36

eissn

0077-8923

issn

1749-6632

pii

1043/1/824

journal_volume

1043

pub_type

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