Nucleoside diphosphate kinases (NDPKs) catalyse the phosphorylation of
nucleoside diphosphates. In mammals, the functional enzyme is a hexam
er composed of different amounts of two homologous acidic (A) and basi
c (B) subunits encoded by separate genes. In prokaryotes and invertebr
ate eukaryotes, only one cytoplasmic enzyme has been isolated. Other g
enes encoding chloroplastic and mitochondrial forms as well as related
proteins have been cloned. Here, we show that in Xenopus laevis, as i
n mammals, the cytoplasmic NDPK is encoded by several homologous genes
. With Xenopus laevis being a pseudotetraploid species, each monomer i
s encoded by two genes. The amino acid sequences are very similar, and
all the differences concern amino acids located at the outer surface
of the hexameric enzyme. The Xenopus genes share 82-87% identity with
their human counterparts. Interestingly, in vitro, the Xenopus X1 enzy
me binds to a specific nuclease hypersensitive element (NHE) of the hu
man c-myc promoter, as does its human counterpart. X1 also binds to a
single-stranded (CT)(n) dinucleotide repeat. The NHE is present in the
coding strand of a pyrimidine-rich region of the 3' non-coding sequen
ce of the Xenopus NDPK genes. We propose that NDPK is indeed able to b
ind to its own mRNA and prevent polyadenylation at the normal position
. This could provide an autoregulatory translation mechanism. A phylog
enetic tree of the vertebrate NDPK sequences supports the idea that in
amphibians, as in mammals, gene duplication has resulted in functiona
l diversification. (C) 1997 Elsevier Science B.V.