c-Jun represses the human insulin promoter activity that depends on multiple cAMP response elements

Journal Article · Sat Feb 01 00:00:00 EST 1992 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.89.3.1045· OSTI ID:5688665

Inagaki, Nobuya; Seino, Yutaka; Imura, Hiroo ^[1]; Maekawa, Toshio; Sudo, Tatsuhiko; Ishii, Shunsuke ^[2]

---

1. Kyoto Univ. (Japan)
2. Inst. of Physical and Chemical Research (RIKEN), Tsukuba (Japan)

Glucose is known to increase the cAMP concentration in pancreatic {beta} cells. To determine the mechanism by which cAMP augments insulin gene expression, the authors first identified the cAMP response elements (CREs) of human insulin gene. In DNase I footprint analysis, the bacterially synthesized CRE-binding protein, CRE-BP1, protected four sites: two sites in the region upstream from the insulin core promoter, one site in the first exon, and one site in the first intron. To examine the roles of those four sites, they constructed a series of DNA plasmids in which the wild-type and mutant insulin promoters were linked to the chloramphenicol acetyltransferase gene. Studies of the transcriptional activity of these plasmids after transfection into hamster insulinoma (HIT) cells showed that these four sites contributed additively to the cAMP inducibility of the insulin promoter. Surprisingly, the c-jun protooncogene product (c-Jun) repressed the cAMP-induced activity of the insulin promoter in a cotransfection assay with the c-Jun expression plasmic. Northern blot analysis demonstrated that the level of c-jun mRNA was dramatically increased by glucose deprivation in HIT cells. These results suggest that glucose deprivation in HIT cells. These results suggest that glucose may regulate expression of the human insulin gene through multiple CREs and c-Jun.

• OSTI ID: 5688665
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 89:3; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
INSULIN
GENE REGULATION
ONCOGENES
DNA HYBRIDIZATION
AMP
DNA-ASE
GENE REPRESSORS
GLUCOSE
MESSENGER-RNA
PANCREAS
PLASMIDS
TRANSFERASES
ALDEHYDES
BODY
CARBOHYDRATES
CELL CONSTITUENTS
DIGESTIVE SYSTEM
ENDOCRINE GLANDS
ENZYMES
ESTERASES
GENES
GLANDS
HEXOSES
HORMONES
HYBRIDIZATION
HYDROLASES
MONOSACCHARIDES
NUCLEIC ACIDS
NUCLEOPROTEINS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHOSPHODIESTERASES
PROTEINS
RNA
SACCHARIDES
550200* - Biochemistry