Identification of a novel effector domain of BIN1 for cancer suppression

Greta L. Lundgaard, Natae E. Daniels, Slovénie Pyndiah, Erica K. Cassimere, Kazi M. Ahmed, Amélie Rodrigue, Daisuke Kihara, Carol B. Post, Daitoku Sakamuro

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Bridging integrator 1 (BIN1) is a nucleocytoplasmic adaptor protein with tumor suppressor properties. The protein interacts with and inhibits the c-MYC transcription factor through the BIN1 MYC-binding domain (MBD). However, in vitro colony formation assays have clearly demonstrated that the MBD is not essential for BIN1-mediated growth arrest. We hypothesized that BIN1 contains a MYC-independent effector domain (MID) for cancer suppression. Because a functionally unique domain frequently contains a distinct structure, the human full-length BIN1 protein was subjected to limited trypsin digestion and the digested peptides were analyzed with Edman sequencing and mass spectrometry. We identified a trypsin-resistant peptide that corresponds to amino acids 146-268 of BIN1. It encompassed part of the BAR region, a putative effector region of BIN1. Computational analysis predicted that the peptide is very likely to exhibit coiled-coil motifs, implying a potential role for this region in sustaining the BIN1 structure and function. Like MBD-deleted BIN1, the trypsin-resistant peptide of BIN1 was predominantly present in the cytoplasm and was sufficient to inhibit cancer growth, regardless of dysregulated c-MYC activity. Our results suggest that the coiled-coil BIN1 BAR peptide encodes a novel BIN1 MID domain, through which BIN1 acts as a MYC-independent cancer suppressor.

Original languageEnglish (US)
Pages (from-to)2992-3001
Number of pages10
JournalJournal of cellular biochemistry
Volume112
Issue number10
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

    Fingerprint

Keywords

  • BIN1
  • c-MYC
  • cancer suppression
  • cytoplasmic localization
  • limited proteolysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lundgaard, G. L., Daniels, N. E., Pyndiah, S., Cassimere, E. K., Ahmed, K. M., Rodrigue, A., Kihara, D., Post, C. B., & Sakamuro, D. (2011). Identification of a novel effector domain of BIN1 for cancer suppression. Journal of cellular biochemistry, 112(10), 2992-3001. https://doi.org/10.1002/jcb.23222