| Autor: |
Joao A. Paulo, Alejandro Rojaa, Inke S. Näthke, Nicholas Loyer, Olesja Popow, Ian P. Newton, Jens Januschke, Michael H. Tatham, Kevin M. Haigis |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| DOI: |
10.1101/258400 |
| Popis: |
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 toAPCmutant phenotypes. Collectively, our results highlight the extent and importance of Wnt-independent APC functions in epithelial biology and disease. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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