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 Steigerwald, K. Articles by Groden, J. Search for Related Content PubMed PubMed Citation Articles by Steigerwald, K. Articles by Groden, J.

---

Cell Cycle, Cell Death, and Senescence

The APC Tumor Suppressor Promotes Transcription-Independent Apoptosis In vitro¹

¹ Department of Molecular Genetics, Biochemistry, and Microbiology and ² Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Joanna Groden, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0524. Phone: 513-558-0088; Fax: 513-558-2794. E-mail: joanna.groden{at}uc.edu

The APC tumor suppressor is found in nonproliferating epithelial cells of the colonic crypts and is mutated in most colorectal tumors. To understand the function of APC in normal epithelium and how its loss leads to tumor formation, we tested whether APC is a mediator of apoptosis using an in vitro assay that monitors caspase-3-mediated cleavage of lamin B protein or a colorimetric substrate in a cell-free Xenopus egg extract. Recombinant APC protein accelerates apoptosis-associated caspase activity independently of ongoing transcription and protein synthesis. Conversely, the addition of mutant APC and immunodepletion of Xenopus APC decelerates apoptosis-associated caspase activity. Acceleration of apoptosis by APC is abolished by the caspase-8 inhibitor Z-IETD-FMK, demonstrating that caspase-8 is an essential component of APC-mediated apoptosis. These results suggest that the induction of apoptosis may be one role of APC in tumor suppression and that this mechanism is independent of ß-catenin-mediated effects on transcription.

This article has been cited by other articles:

				M. Brocardo, Y. Lei, A. Tighe, S. S. Taylor, M. T. S. Mok, and B. R. Henderson Mitochondrial Targeting of Adenomatous Polyposis Coli Protein Is Stimulated by Truncating Cancer Mutations: REGULATION OF Bcl-2 AND IMPLICATIONS FOR CELL SURVIVAL J. Biol. Chem., February 29, 2008; 283(9): 5950 - 5959. [Abstract] [Full Text] [PDF]