Insulin-like growth factors (IGFs) belong to a family of growth factors with structural homology to proinsulin. Up till now, no specific details regarding the transcriptional regulation by autocrine, paracrine or endocrine effector molecules
in vivo have been described for the
IGF-II gene. This is in big contrast to
IGF-I gene transcription which has been studied more extensively. To better understand how the
IGF-II gene is controlled at the gene transcription level, we have isolated the common carp
IGF-II gene together with the 5′-flanking region by genomic library screening. The mature IGF-II protein was encoded by exon 2 and exon 3. Transient transfection of the 5′-flanking region containing a TATA box-like sequence into cultured eukaryotic cells revealed that it is a strong
promoter with definitive tissue specificity. Nucleotides between − 301 and − 62 in the
promoter are essential to drive the basal
IGF-II gene expression; whereas nucleotides between − 891 and − 416 in the
promoter are responsible for the growth hormone activation. Using electrophoretic mobility shift assay and yeast one-hybrid screening, it was demonstrated that
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1-antitrypsin could bind specifically to the nucleotide position − 301 to − 262 of the gene
promoter. Co-transfection studies revealed that the over-expression of
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1-antitrypsin increased the
IGF-II promoter activity by 3.4-fold, further confirming that
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1-antitrypsin acts as a
trans-acting factor on the
IGF-II promoter.