RT Journal Article
SR Electronic
T1 Identification of endogenous Adenomatous polyposis coli interaction partners and β-catenin-independent targets by proteomics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 258400
DO 10.1101/258400
A1 Olesja Popow
A1 Michael H. Tatham
A1 João A. Paulo
A1 Alejandro Rojas-Fernandez
A1 Nicolas Loyer
A1 Ian P. Newton
A1 Jens Januschke
A1 Kevin M. Haigis
A1 Inke Näthke
YR 2018
UL http://biorxiv.org/content/early/2018/02/01/258400.abstract
AB Adenomatous 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.