SNIP1 Is a Candidate Modifier of the Transcriptional Activity of c-Myc on E Box-Dependent Target Genes

Makiko Fujii, Lyudmila A. Lyakh, Cameron P P. Bracken, Junya Fukuoka, Morisada Hayakawa, Tadasuke Tsukiyama, Steven J J. Soll, Melissa Harris, Sonia Rocha, Kevin C C. Roche, Shin ichi Tominaga, Jin Jen, Neil D D. Perkins, Robert J. Lechleider, Anita B B. Roberts

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Using a yeast two-hybrid screen, we found that SNIP1 (Smad nuclear-interacting protein 1) associates with c-Myc, a key regulator of cell proliferation and transformation. We demonstrate that SNIP1 functions as an important regulator of c-Myc activity, binding the N terminus of c-Myc through its own C terminus, and that SNIP1 enhances the transcriptional activity of c-Myc both by stabilizing it against proteosomal degradation and by bridging the c-Myc/p300 complex. These effects of SNIP1 on c-Myc likely contribute to synergistic effects of SNIP1, c-Myc, and H-Ras in inducing formation of foci in an in vitro transformation assay and also in supporting anchorage-independent growth. The significant association of SNIP1 and c-Myc staining in a non-small cell lung cancer tissue array is further evidence that their activities might be linked and suggests that SNIP1 might be an important modulator of c-Myc activity in carcinogenesis.

Original languageEnglish (US)
Pages (from-to)771-783
Number of pages13
JournalMolecular Cell
Volume24
Issue number5
DOIs
StatePublished - Dec 8 2006

Keywords

  • CELLCYCLE
  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Fujii, M., Lyakh, L. A., Bracken, CP. P., Fukuoka, J., Hayakawa, M., Tsukiyama, T., Soll, SJ. J., Harris, M., Rocha, S., Roche, KC. C., Tominaga, S. I., Jen, J., Perkins, ND. D., Lechleider, R. J., & Roberts, AB. B. (2006). SNIP1 Is a Candidate Modifier of the Transcriptional Activity of c-Myc on E Box-Dependent Target Genes. Molecular Cell, 24(5), 771-783. https://doi.org/10.1016/j.molcel.2006.11.006