HSP105 recruits protein phosphatase 2A to dephosphorylate β-catenin.
作者： Nancy Yu , Michael Kakunda , Victoria Pham , Jennie R. Lill , Pan Du
DOI: 10.1128/MCB.01307-14
关键词:
摘要: The Wnt/β-catenin pathway causes accumulation of β-catenin in the cytoplasm and its subsequent translocation into nucleus to initiate transcription target genes. Without Wnt stimulation, forms a complex with axin (axis inhibitor), adenomatous polyposis coli (APC), casein kinase 1α (CK1α), glycogen synthase 3β (GSK3β) undergoes phosphorylation-dependent ubiquitination. Phosphatases, such as protein phosphatase 2A (PP2A), interestingly, also are components this degradation complex; therefore, balance must be reached between phosphorylation dephosphorylation. How is regulated largely unknown. Here we show that heat shock protein, HSP105, previously unidentified component complex. HSP105 required for signaling, since depletion compromises gene upon stimulation. Mechanistically, disrupts integration PP2A complex, favoring hyperphosphorylation β-catenin. overexpressed many types tumors, correlating increased nuclear levels upregulation. Furthermore, overexpression prognostic biomarker correlates poor overall survival breast cancer patients well melanoma participating BRIM2 clinical study.
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