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Identification of a novel effector domain of BIN1 for cancer suppression
Author(s) -
Lundgaard Greta L.,
Daniels Natae E.,
Pyndiah Slovénie,
Cassimere Erica K.,
Ahmed Kazi M.,
Rodrigue Amélie,
Kihara Daisuke,
Post Carol B.,
Sakamuro Daitoku
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23222
Subject(s) - effector , biology , edman degradation , trypsin , peptide , microbiology and biotechnology , cytoplasm , peptide sequence , biochemistry , gene , enzyme
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. J. Cell. Biochem. 112: 2992–3001, 2011. © 2011 Wiley‐Liss, Inc.