This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DuHadaway, J. B. Articles by Prendergast, G. C. Search for Related Content PubMed PubMed Citation Articles by DuHadaway, J. B. Articles by Prendergast, G. C.

Bin1 Mediates Apoptosis by c-Myc in Transformed Primary Cells¹

The Wistar Institute, Philadelphia, Pennsylvania 19104 [J. B. D., D. S., D. L. E., G. C. P.], and Glenolden Laboratory, DuPont Pharmaceuticals Company, Glenolden, Pennsylvania 19036 [J. B. D., G. C. P.]

The Bin1 gene encodes a c-Myc-interacting adapter protein with tumor suppressor and cell death properties. In this study, we offer evidence that Bin1 participates in a mechanism through which c-Myc activates programmed cell death in transformed primary chick or rat cells. Antisense or dominant inhibitory Bin1 genes did not affect the ability of c-Myc to drive proliferation or transformation, but they did reduce the susceptibility of cells to c-Myc-induced apoptosis. Protein-protein interaction was implicated, suggesting that Bin1 mediates a death or death sensitization signal from c-Myc. Our findings offer direct support for the "dual signal" model of Myc apoptotic function, based on interactions with a binding protein. Loss of Bin1 in human tumors may promote malignant progression in part by helping to stanch the death penalty associated with c-Myc activation.

This article has been cited by other articles:

				R. S.Y. Cheung, J. T. Brooling, M. M. Johnson, K. J. Riehle, J. S. Campbell, and N. Fausto Interactions between MYC and transforming growth factor alpha alter the growth and tumorigenicity of liver progenitor cells Carcinogenesis, December 1, 2007; 28(12): 2624 - 2631. [Abstract] [Full Text] [PDF]

				G. Grelle, S. Kostka, A. Otto, B. Kersten, K. F. Genser, E.-C. Muller, S. Walter, A. Boddrich, U. Stelzl, C. Hanig, et al. Identification of VCP/p97, Carboxyl Terminus of Hsp70-interacting Protein (CHIP), and Amphiphysin II Interaction Partners Using Membrane-based Human Proteome Arrays Mol. Cell. Proteomics, February 1, 2006; 5(2): 234 - 244. [Abstract] [Full Text] [PDF]

				T. Tajiri, X. Liu, P. M. Thompson, S. Tanaka, S. Suita, H. Zhao, J. M. Maris, G. C. Prendergast, and M. D. Hogarty Expression of a MYCN-interacting Isoform of the Tumor Suppressor BIN1 Is Reduced in Neuroblastomas with Unfavorable Biological Features Clin. Cancer Res., August 1, 2003; 9(9): 3345 - 3355. [Abstract] [Full Text] [PDF]

				A. J. Muller, J. F. Baker, J. B. DuHadaway, K. Ge, G. Farmer, P. S. Donover, R. Meade, C. Reid, R. Grzanna, A. H. Roach, et al. Targeted Disruption of the Murine Bin1/Amphiphysin II Gene Does Not Disable Endocytosis but Results in Embryonic Cardiomyopathy with Aberrant Myofibril Formation Mol. Cell. Biol., June 15, 2003; 23(12): 4295 - 4306. [Abstract] [Full Text] [PDF]

				B. Zech, A. Kurtenbach, N. Krieger, D. Strand, S. Blencke, M. Morbitzer, K. Salassidis, M. Cotten, J. Wissing, S. Obert, et al. Identification and characterization of amphiphysin II as a novel cellular interaction partner of the hepatitis C virus NS5A protein J. Gen. Virol., March 1, 2003; 84(3): 555 - 560. [Abstract] [Full Text] [PDF]

				M. B. Genter, D. M. Burman, S. Vijayakumar, C. L. Ebert, and B. J. Aronow Genomic analysis of alachlor-induced oncogenesis in rat olfactory mucosa Physiol Genomics, December 26, 2002; 12(1): 35 - 45. [Abstract] [Full Text] [PDF]

				M. Couillard, R. Guillaume, N. Tanji, V. D'Agati, and M. Trudel c-myc-induced Apoptosis in Polycystic Kidney Disease Is Independent of FasL/Fas Interaction Cancer Res., April 1, 2002; 62(8): 2210 - 2214. [Abstract] [Full Text] [PDF]