XIHbox 8, an endoderm-specific Xenopus homeodomain protein, is closely related to a mammalian insulin gene transcription factor.

Peshavaria M, Gamer L, Henderson E, Teitelman G, Wright CV, Stein R
Mol Endocrinol. 1994 8 (6): 806-16

PMID: 7935494 · DOI:10.1210/mend.8.6.7935494

The cis-acting sequences that mediate insulin gene expression exclusively in pancreatic islet beta-cells are localized within the 5'-flanking region between nucleotides -340 and -91. We have identified an evolutionarily conserved, A+T-rich element at -201/-196 basepairs in the rat insulin II gene that is essential for efficient expression in beta-cells. Affinity-purified antibody to the XIHbox 8 protein super-shifted the major beta-cell-activator factor complex binding to the -201/-196 element. XIHbox 8 is a Xenopus endoderm-specific homeodomain protein whose expression is restricted to the nucleus of endodermal cells of the duodenum and developing pancreas. Antibody to XIHbox 8 specifically interacts with a 47-kilodalton protein present in this DNA complex. Immunohistochemical studies revealed XIHbox 8-like proteins within the nucleus of almost all mouse islet beta-cells and a subset of islet alpha- and beta-cells. These results are consistent with the proposal that an XIHbox 8-related homeoprotein of 47 kilodalton is required for expression of the mammalian insulin gene in beta-cells. Experiments conducted with antiserum raised to somatostatin transcription factor-1 (STF-1), a recently isolated mammalian XIHbox 8-related homeoprotein, indicate that the STF-1 protein is the mammalian homolog of Xenopus XIHbox 8.

MeSH Terms (25)

Amino Acid Sequence Animals Base Sequence Blotting, Western Cell Nucleus Cricetinae DNA Electrophoresis, Polyacrylamide Gel Genes, Homeobox Homeodomain Proteins Immunohistochemistry Insulin Insulinoma Islets of Langerhans Mice Molecular Sequence Data Pancreatic Neoplasms Rats Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Somatostatin Transcription Factors Tumor Cells, Cultured Xenopus Xenopus Proteins

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