John Poulton
2009-Present |
How does the tumor
suppressor APC regulate the cytoskeleton? |
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Adenomatous Polyposis Coli (APC) proteins are tumor suppressor proteins that regulate both Wnt signaling and the cytoskeleton during both normal development and oncogenesis. Although much attention has been paid to APC’s role in Wnt signaling, APC also has Wnt-independent cytoskeletal functions of APC that may be relevant for APC’s role in cancer biology. For example, APC proteins are linked to mitotic spindle orientation, spindle attachment, and prevention of chromosomal instability (CIN); defects in any of these cytoskeletal events may promote cancer initiation or progression. Thus, the oncogenic effect of compromised APC function may reside in its contributions to both Wnt signaling and cytoskeletal processes. |
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How APC regulates the cytoskeleton is not well understood. In the cases of spindle orientation and attachment, it was proposed that APC localization and interaction with microtubules (MTs) and cortical actin are essential. The mechanisms underlying increased CIN due to APC loss are even more uncertain, but various reports suggest they may stem from defects in MT dynamics, kinetochore attachments, or spindle assembly checkpoint activity. I am using Drosophila APC2 as a model to investigate these putative functions of APC proteins. A more complete understanding of APC’s involvement in cytoskeletal regulation will greatly improve our ability to assess and interpret APC’s significance in both normal development and carcinogenesis. |
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Publications Roberts,D.M., Pronobis, M.I., Poulton, J.S., Waldmann, J.D., Stephenson, E.M., Hanna, S., and Peifer, M. (2011). Deconstructing the ßcatenin destruction complex: mechanistic roles for the tumor suppressor APC in regulating Wnt signaling. Molecular Biology of the Cell, in press. The microRNA pathway regulates the temporal pattern of Notch signaling
in Drosophila follicle cells. (2011) Poulton JS, Huang
YC, Smith L, Sun J, Leake N, Schleede J, Stevens LM, Deng WM. Tamori Y, Bialucha C, Tian A, Kajita M, Huang YC, Norman M, Harrison N, Poulton J, Ivanovitch K, Disch L, Liu T, Deng W-M, and Y Fujita. (2010) Involvement of Lgl and Mahjong/VprBP in Cell Competition PLoS Biology 8(7): e1000422 Sagona AP, Nezis IP, Pedersen NM, Liestøl K, Poulton JS, Rusten TE, Skotheim RI, Raiborg C, and Stenmark H. (2010) “PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody” Nature Cell Biology March 7:1-12 Yu J*, Poulton J*, Huang YC, and W-M Deng. (2008) “The Hippo pathway promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity” PLoS One 3(3):e1761 *equal contribution Poulton J and W-M Deng. (2007) “Cell–cell communication and axis specification in the Drosophila oocyte” Developmental Biology 311(1):1-10 Schneider M, Khalil AA, Poulton J, Castillejo-Lopez C, Egger-Adam D, Wodarz A, Deng W-M, and S Baumgartner. (2006) “Perlecan and Dystroglycan act at the basal side of the Drosophila follicular epithelium to maintain epithelial organization” Development 133(19):3805-3815 Poulton J and W-M Deng. (2006) “Dystroglycan down-regulation links EGF receptor signaling and anterior-posterior polarity formation in the Drosophila oocyte” Proceedings of the National Academy of Sciences USA 103(34):12775-12780 Poulton J and A Winn. (2002) “Costs of canalization and plasticity in response to neighbors in Brassica rapa” Plant Species Biology 17:109-118 |