Bin1 functionally interacts with Myc and inhibits cell proliferation via multiple mechanisms

Katherine Elliott, Daitoku Sakamuro, Amithaba Basu, Wei Du, William Wunner, Peter Staller, Stefan Gaubatz, Hong Zhang, Edward Prochownik, Martin Eilers, George C. Prendergast

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

The tumor suppressor Bin1 was identified through its interaction with the N-terminal region of Myc which harbors its transcriptional activation domain. Here we show that Bin1 and Myc physically and functionally associate in cells and that Bin1 inhibits cell proliferation through both Myc-dependent and Myc-independent mechanisms. Bin1 specifically inhibited transactivation by Myc as assayed from artificial promoters or from the Myc target genes ornithine decarboxylase (ODC) and α prothymosin (pT). Inhibition of ODC but not pT required the presence of the Myc binding domain (MBD) of Bin1 suggesting two mechanisms of action. Consistent with this possibility, a non-MBD region of Bin1 was sufficient to recruit a repression function to DNA that was unrelated to histone deacetylase. Regions outside the MBD required for growth inhibition were mapped in Ras cotransformation or HepG2 hepatoma cell growth assays. Bin1 required the N-terminal BAR domain to suppress focus formation by Myc whereas the C-terminal U1 and SH3 domains were required to inhibit adenovirus E1A or mutant p53, respectively. All three domains contributed to Bin1 suppression of tumor cell growth hut BAR-C was most crucial. These findings supported functional interaction between Myc and Bin1 in cells and indicated that Bin1 could inhibit malignant cell growth through multiple mechanisms.

Original languageEnglish (US)
Pages (from-to)3564-3573
Number of pages10
JournalOncogene
Volume18
Issue number24
DOIs
StatePublished - Jun 17 1999
Externally publishedYes

Keywords

  • Transcription
  • Transformation
  • Tumor supressor
  • c-Myc

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Elliott, K., Sakamuro, D., Basu, A., Du, W., Wunner, W., Staller, P., Gaubatz, S., Zhang, H., Prochownik, E., Eilers, M., & Prendergast, G. C. (1999). Bin1 functionally interacts with Myc and inhibits cell proliferation via multiple mechanisms. Oncogene, 18(24), 3564-3573. https://doi.org/10.1038/sj.onc.1202670