Cloning of the mouse insulin receptor substrate-3 (mirs-3) promoter, and its regulation by p53. (Articolo in rivista)

Type
Label
  • Cloning of the mouse insulin receptor substrate-3 (mirs-3) promoter, and its regulation by p53. (Articolo in rivista) (literal)
Anno
  • 2002-01-01T00:00:00+01:00 (literal)
Alternative label
  • Sciacchitano S., Orecchio A., Lavra L., Misiti S., Giacchini A., Zani M., Danese D., Gurtner A., Soddu S., Di Mario U., Andreoli M. (2002)
    Cloning of the mouse insulin receptor substrate-3 (mirs-3) promoter, and its regulation by p53.
    in Molecular endocrinology (Baltim. Md.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Sciacchitano S., Orecchio A., Lavra L., Misiti S., Giacchini A., Zani M., Danese D., Gurtner A., Soddu S., Di Mario U., Andreoli M. (literal)
Pagina inizio
  • 1577 (literal)
Pagina fine
  • 1589 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 16 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Cloning of the mouse insulin receptor substrate-3 (mirs-3) promoter, and its regulation by p53. (literal)
Abstract
  • The insulin receptor susbtrate-3 (IRS-3) is a member of a family of intermediate adapter proteins that function as major intracellular targets for phosphorylation by the activated insulin and IGF-I receptors. Among the 4 IRS proteins identified so far, IRS-3 exhibits a rather peculiar expression pattern during both the embryonic development and adult life, suggesting a different mechanism of regulation of its expression. In this study, we cloned the 5’ flanking region of the mIRS-3 gene and analyzed its promoter activity. The mIRS-3 promoter is inhibited by wt p53 and this effect is completely abolished by co-transfection of a dominant negative p53. Tumor-derived p53 mutants show variable, but lower suppressing capability than wt p53. In addition, treatment with Doxorubicin inhibits endogenous expression of mIRS-3 mRNA in C2C12 and 3T3-L1 cells. The DNA region spanning from nt –287 and –178 in the mIRS-3 promoter is responsible for a 32.2% reduction of the MDM2 promoter activity, suggesting its involvement in the p53-mediated inhibitory effect. In conclusion, our study demonstrates that the mIRS-3 promoter is regulated by p53 at the transcriptional level. The inhibition of mIRS-3 promoter by wt p53, and its de-repression by tumor-derived p53 mutants, appears to be similar to that previously reported for the IGF-I receptor promoter, suggesting a common role of these two genes in p53-mediated cell growth and differentiation. (literal)
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