A MAJOR ESTROGEN-REGULATED PROTEIN SECRETED FROM THE LIVER OF XENOPUS-LAEVIS IS A MEMBER OF THE SERPIN SUPERFAMILY - NUCLEOTIDE-SEQUENCE OFCDNA AND HORMONAL INDUCTION OF MESSENGER-RNA
Lj. Holland et al., A MAJOR ESTROGEN-REGULATED PROTEIN SECRETED FROM THE LIVER OF XENOPUS-LAEVIS IS A MEMBER OF THE SERPIN SUPERFAMILY - NUCLEOTIDE-SEQUENCE OFCDNA AND HORMONAL INDUCTION OF MESSENGER-RNA, The Journal of biological chemistry, 267(10), 1992, pp. 7053-7059
Estrogen treatment of Xenopus frogs causes four mRNAs to become highly
abundant in the liver. Three of these mRNAs have been previously iden
tified as coding for vitellogenin, ferritin, and serum retinol binding
protein. We show here that the fourth abundant liver messenger RNA co
mprises about 1500 nucleotides and codes for a 45-kDa secreted protein
, designated Ep45. A clone complementary to Ep45 mRNA was isolated, an
d its identity was confirmed by hybridization selection of mRNA that t
ranslated in vitro into the Ep45 precursor. Nucleotide sequence analys
is of the nearly full length cDNA revealed a total length of 1454 base
pairs consisting of: 36 nucleotides of the 5' noncoding region, 1308
base pairs encoding an open reading frame of 436 amino acids, and 110
nucleotides of the 3' untranslated region. Ep45 mRNA may originate fro
m as many as four closely spaced transcription start sites, which are
15 to 21 bases upstream of the first nucleotide of the cDNA clone. The
Xenopus laevis genome appears to contain a single Ep45 gene. The dedu
ced amino acid sequence indicates that Ep45 has features typical of a
secreted protein, including a signal peptide of 16 amino acids and thr
ee potential sites for N-linked glycosylation, and is related to the s
erine protease inhibitors, a large family of proteins with very divers
e physiological functions. Ep45 mRNA was absent in the liver of normal
male frogs and increased at least 100-fold in response to estradiol-1
7-beta. Thus, both Ep45 and vitellogenin mRNAs are switched from undet
ectable to very high levels, a pattern of expression not found for any
other mRNAs in Xenopus liver.