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PXD056028

PXD056028 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleWnt signaling inhibits Casein kinase 1a activity by modulating its interaction with Protein phosphatase 2A
DescriptionThe mechanism by which Wnt signaling, an essential pathway controlling development and disease, stabilizes beta-Catenin has been a subject of debate over the last three decades. Casein kinase 1alpha (CK1a) functions as a pivotal negative regulator of this signaling pathway, initiating the events that destabilize beta-Catenin. However, whether and how CK1a activity is regulated in Wnt-off and Wnt-on states remains poorly understood. We now show that CK1a activity requires its association with the alpha catalytic subunit of Protein phosphatase 2A (PPP2CA) on AXIN, the scaffold protein of the beta-Catenin destruction complex. Wnt stimulation induces the dissociation of PPP2CA from CK1a, resulting in CK1a autophosphorylation and its consequent inactivation. Moreover, autophosphorylated CK1a is enriched in a subset of colorectal cancers (CRC) harboring constitutive Wnt activation. Our findings identify a novel mechanism by which Wnt stimulation inactivates CK1a, filling a critical gap in our understanding of Wnt signaling, with relevance for CRC.
HostingRepositoryMassIVE
AnnounceDate2026-02-20
AnnouncementXMLSubmission_2026-02-20_11:07:37.520.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHsin-Yao Tang
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListPhospho
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-09-19 09:56:04ID requested
12026-02-20 11:07:38announced
Publication List
Shen C, Lu W, Merugu SB, Bharti A, Afify SM, Schnitkey L, Wynn DT, Yang F, Rohwetter TM, Nayak A, Bunnag N, Cywiak C, Tang HY, Harris BT, Albanese C, Ihemelandu C, Cobb MH, Kettenbach A, Lee E, Ahmed Y, Robbins DJ, activity by modulating its interaction with protein phosphatase 2A. Cell Rep, 44(2):115274(2025) [pubmed]
Keyword List
submitter keyword: CK1a, Wnt signaling, Protein phosphatase 2A, autophosphorylation, colorectal cancer
Contact List
David J. Robbins
contact affiliationDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University
contact emaildr956@georgetown.edu
lab head
Hsin-Yao Tang
contact affiliationThe Wistar Institute
contact emailtangh@wistar.org
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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