Interaction between Tumor Suppressor Adenomatous Polyposis Coli and Topoisomerase IIα: Implication for the G2/M Transition
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Issue Date
2008-10-01Author
Wang, Yang
Azuma, Yoshiaki
Moore, David S.
Osheroff, Neil
Neufeld, Kristi L.
Publisher
American Society for Cell Biology
Type
Article
Article Version
Scholarly/refereed, publisher version
Metadata
Show full item recordAbstract
The tumor suppressor adenomatous polyposis coli (APC) is implicated in regulating multiple stages of the cell cycle. APC participation in G1/S is attributed to its recognized role in Wnt signaling. APC function in the G2/M transition is less well established. To identify novel protein partners of APC that regulate the G2/M transition, APC was immunoprecipitated from colon cell lysates and associated proteins were analyzed by matrix-assisted laser desorption ionization/time of flight (MALDI-TOF). Topoisomerase IIα (topo IIα) was identified as a potential binding partner of APC. Topo IIα is a critical regulator of G2/M transition. Evidence supporting an interaction between endogenous APC and topo IIα was obtained by coimmunoprecipitation, colocalization, and Förster resonance energy transfer (FRET). The 15-amino acid repeat region of APC (M2-APC) interacted with topo IIα when expressed as a green fluorescent protein (GFP)-fusion protein in vivo. Although lacking defined nuclear localization signals (NLS) M2-APC predominantly localized to the nucleus. Furthermore, cells expressing M2-APC displayed condensed or fragmented nuclei, and they were arrested in the G2 phase of the cell cycle. Although M2-APC contains a β-catenin binding domain, biochemical studies failed to implicate β-catenin in the observed phenotype. Finally, purified recombinant M2-APC enhanced topo IIα activity in vitro. Together, these data support a novel role for APC in the G2/M transition, potentially through association with topo IIα.
Description
This is the publisher's version, also available electronically from http://www.molbiolcell.org/content/19/10/4076
ISSN
1059-1524Collections
Citation
Wang, Yang et al. (2008). "Interaction between Tumor Suppressor Adenomatous Polyposis Coli and Topoisomerase IIα: Implication for the G2/M Transition." Molecular Biology of the Cell, 19(10):4076-86. http://www.dx.doi.org/10.1091/mbc.E07-12-1296
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