Introduction
Results
Chemical cross-linking coupled to mass spectrometry shows that the CIP2A N-terminal head domain mediates B56α binding

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N-terminal head domain of CIP2A stabilizes full-length CIP2A protein in cancer cells

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Single amino acid mutation on the N-terminal head domain of CIP2A abrogates TNBC tumorigenicity

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CIP2A hijacks B56α and PP2Ac from the PP2A-B56α heterotrimer

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CIP2A mutes LxxIxE motif-dependent substrate binding to B56α

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Validation of the “hijack and mute” model of PP2A-B56α inhibition by CIP2A in cellulo

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To substantiate these conclusions, we validated the impact of N-terminal K21A mutation on phosphorylation of LxxIxE-motif containing proteins. Comparison of LC-MS analyzed phosphoproteomes between the control clone and CIP2A K21A clone 1 (both in triplicates) resulted in identification of 78 phosphopeptides from 63 individual proteins that were significantly (FDR < 0.05) downregulated in CIP2A K21A cells (Supplementary Data3