c-jun inhibits insulin control element-mediated transcription by affecting the transactivation potential of the E2A gene products.

Robinson GL, Henderson E, Massari ME, Murre C, Stein R
Mol Cell Biol. 1995 15 (3): 1398-404

PMID: 7862133 · PMCID: PMC230364 · DOI:10.1128/mcb.15.3.1398

Pancreatic beta-cell-type-specific transcription of the insulin gene is principally controlled by trans-acting factors which influence insulin control element (ICE)-mediated expression. The ICE activator is composed, in part, of the basic helix-loop-helix proteins E12, E47, and E2-5 encoded by the E2A gene. Previous experiments showed that ICE activation in beta cells was repressed in vivo by the c-jun proto-oncogene (E. Henderson and R. Stein, Mol. Cell. Biol. 14:655-662, 1994). Here we focus on the mechanism by which c-Jun inhibits ICE-mediated activation. c-Jun was shown to specifically repress the transactivation potential of the E2A proteins. Thus, we found that the activity of GAL4:E2A fusion constructs was inhibited by c-Jun. The transrepression capabilities of c-Jun were detected only in pancreatic islet cell lines that contained a functional ICE activator. Repression of GAL4:E2A was mediated by the basic leucine zipper regions of c-Jun, which are also the essential regions of this protein necessary for controlling ICE activator-stimulated expression in vivo. The specific target of c-Jun repression was the transactivation domain (located between amino acids 345 and 408 in E12 and E47) conserved in E12, E47, and E2-5. In contrast, the activation domain unique to the E12 and E47 proteins (located between amino acids 1 and 99) was unresponsive to c-Jun. Our results indicate that c-Jun inhibits insulin gene transcription in beta cells by reducing the transactivation potential of the E2A proteins present in the ICE activator complex.

MeSH Terms (20)

Adenoviridae Adenovirus E2 Proteins Animals Base Sequence Cell Line Cricetinae DNA Primers Gene Expression Regulation Genes, jun HeLa Cells Humans Insulin Islets of Langerhans Mice Molecular Sequence Data Polymerase Chain Reaction Proto-Oncogene Proteins c-jun Transcription, Genetic Transcriptional Activation Transfection

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