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 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.

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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