scholarly journals Identification of endogenous Adenomatous polyposis coli interaction partners and β-catenin-independent targets by proteomics

2018 ◽  
Author(s):  
Olesja Popow ◽  
Michael H. Tatham ◽  
João A. Paulo ◽  
Alejandro Rojas-Fernandez ◽  
Nicolas Loyer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Adenomatous Polyposis Coli ◽  
Wnt Signaling Pathway ◽  
Potential Contribution ◽  
Adenomatous Polyposis ◽  
Label Free ◽  
Polyposis Coli ◽  
Affinity Enrichment ◽  
Interaction Partners ◽  
Mutant Phenotypes

SummaryAdenomatous polyposis coli (APC) is the most frequently mutated gene in colorectal cancer. APC negatively regulates the pro-proliferative Wnt signaling pathway by promoting the degradation of β-catenin, but the extent to which APC exerts Wnt/β-catenin-independent tumor suppressive activity is unclear. To identify interaction partners and β-catenin-independent targets of endogenous, full-length APC, we applied label-free and multiplexed TMT mass spectrometry. Affinity enrichment-mass spectrometry revealed over 150 previously unidentified APC interaction partners. Moreover, our global proteomic analysis revealed that roughly half of the protein expression changes that occur in response to APC loss are independent of β-catenin. By combining these two analyses, we identified Misshapen-like kinase 1 (MINK1) as a putative substrate of an alternative APC-containing destruction complex and provide evidence for the potential contribution of MINK1 to APC mutant phenotypes. Collectively, our results highlight the extent and importance of Wnt-independent APC functions in epithelial biology and disease.

Identification of Eendogenous Adenomatous Polyposis Coli Interaction Partners and β-Catenin-Independent Targets by Proteomics

2018 ◽  
Author(s):  
Olesja Popow ◽  
Michael H. Tatham ◽  
Jooo A. Paulo ◽  
Alejandro Rojas-Fernandez ◽  
Nicolas Loyer ◽  
...  
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Interaction Partners

scholarly journals Destruction Complex Function in the Wnt Signaling Pathway of Drosophila Requires Multiple Interactions Between Adenomatous Polyposis Coli 2 and Armadillo

Genetics ◽  
2011 ◽  
Vol 190 (3) ◽  
pp. 1059-1075 ◽  
Author(s):  
Ezgi Kunttas-Tatli ◽  
Meng-Ning Zhou ◽  
Sandra Zimmerman ◽  
Olivia Molinar ◽  
Fangyuan Zhouzheng ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Adenomatous Polyposis Coli ◽  
Complex Function ◽  
Wnt Signaling Pathway ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Multiple Interactions

scholarly journals The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling

2015 ◽  
Vol 26 (24) ◽  
pp. 4503-4518 ◽  
Author(s):  
Ezgi Kunttas-Tatli ◽  
Ryan A. Von Kleeck ◽  
Bradford D. Greaves ◽  
David Vinson ◽  
David M. Roberts ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Wnt Signaling ◽  
Adenomatous Polyposis Coli ◽  
Complex Function ◽  
Wnt Signaling Pathway ◽  
Sequence Conservation ◽  
Binding Motif ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Suppressor Activity

The tumor suppressor Adenomatous polyposis coli (APC) plays a key role in regulating the canonical Wnt signaling pathway as an essential component of the β-catenin destruction complex. C-terminal truncations of APC are strongly implicated in both sporadic and familial forms of colorectal cancer. However, many questions remain as to how these mutations interfere with APC’s tumor suppressor activity. One set of motifs frequently lost in these cancer-associated truncations is the SAMP repeats that mediate interactions between APC and Axin. APC proteins in both vertebrates and Drosophila contain multiple SAMP repeats that lack high sequence conservation outside of the Axin-binding motif. In this study, we tested the functional redundancy between different SAMPs and how these domains are regulated, using Drosophila APC2 and its two SAMP repeats as our model. Consistent with sequence conservation–based predictions, we show that SAMP2 has stronger binding activity to Axin in vitro, but SAMP1 also plays an essential role in the Wnt destruction complex in vivo. In addition, we demonstrate that the phosphorylation of SAMP repeats is a potential mechanism to regulate their activity. Overall our findings support a model in which each SAMP repeat plays a mechanistically distinct role but they cooperate for maximal destruction complex function.

scholarly journals The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells

2002 ◽  
Vol 157 (6) ◽  
pp. 1041-1048 ◽  
Author(s):  
Mette M. Mogensen ◽  
John B. Tucker ◽  
John B. Mackie ◽  
Alan R. Prescott ◽  
Inke S. Näthke
Keyword(s):  
Epithelial Cells ◽  
Adenomatous Polyposis Coli ◽  
Wnt Signaling Pathway ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Cytoskeletal Organization ◽  
Cell Biol ◽  
Polarized Epithelial Cells ◽  
Apc Protein

Loss of full-length adenomatous polyposis coli (APC) protein correlates with the development of colon cancers in familial and sporadic cases. In addition to its role in regulating β-catenin levels in the Wnt signaling pathway, the APC protein is implicated in regulating cytoskeletal organization. APC stabilizes microtubules in vivo and in vitro, and this may play a role in cell migration (Näthke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, and W.J. Nelson. 1996. J. Cell Biol. 134:165–179; Mimori-Kiyosue, Y., N. Shiina, and S. Tsukita. 2000. J. Cell Biol. 148:505–517; Zumbrunn, J., K. Inoshita, A.A. Hyman, and I.S. Näthke. 2001. Curr. Biol. 11:44–49) and in the attachment of microtubules to kinetochores during mitosis (Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C. Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001. Nat. Cell Biol. 3:433–438; Kaplan, K.B., A. Burds, J.R. Swedlow, S.S. Bekir, P.K. Sorger, and I.S. Näthke. 2001. Nat. Cell Biol. 3:429–432). The localization of endogenous APC protein is complex: actin- and microtubule-dependent pools of APC have been identified in cultured cells (Näthke et al., 1996; Mimori-Kiyosue et al., 2000; Reinacher-Schick, A., and B.M. Gumbiner. 2001. J. Cell Biol. 152:491–502; Rosin-Arbesfeld, R., G. Ihrke, and M. Bienz. 2001. EMBO J. 20:5929–5939). However, the localization of APC in tissues has not been identified at high resolution. Here, we show that in fully polarized epithelial cells from the inner ear, endogenous APC protein associates with the plus ends of microtubules located at the basal plasma membrane. Consistent with a role for APC in supporting the cytoskeletal organization of epithelial cells in vivo, the number of microtubules is significantly reduced in apico-basal arrays of microtubule bundles isolated from mice heterozygous for APC.

scholarly journals Identification of Endogenous Adenomatous Polyposis Coli Interaction Partners and β-Catenin–Independent Targets by Proteomics

2019 ◽  
Vol 17 (9) ◽  
pp. 1828-1841
Author(s):  
Olesja Popow ◽  
João A. Paulo ◽  
Michael H. Tatham ◽  
Melanie S. Volk ◽  
Alejandro Rojas-Fernandez ◽  
...  
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Interaction Partners
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