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PXD020478 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer
DescriptionWnt/b-catenin signaling is a primary pathway for stem cell maintenance during tissue renewal and a frequent target for mutations in cancer. Impaired Wnt receptor endocytosis due to loss of the ubiquitin ligase RNF43 gives rise to Wnt-hypersensitive tumors that are susceptible to anti-Wnt-based therapy. Contrary to this paradigm, we identify a class of RNF43 truncating cancer mutations that induce b-catenin-mediated transcription, despite exhibiting retained Wnt receptor downregulation. These mutations interfere with an ubiquitin-independent suppressor role of the RNF43 cytosolic tail that involves casein kinase-1 (CK1) binding and phosphorylation. Mechanistically, truncated RNF43 variants trap CK1 at the plasma membrane, thereby preventing b-catenin turnover and propelling ligandindependent target gene transcription. Gene editing of human colon stem cells shows that RNF43 truncations cooperate with p53 loss to drive a niche-independent program for self-renewal and proliferation. Moreover, these RNF43 variants confer decreased sensitivity to anti-Wnt-based therapy. Our data demonstrate the relevance of studying patient-derived mutations for understanding disease mechanisms and improved applications of precision medicine.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKaterina Hanakova
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListbiotinylated residue; phosphorylated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-07-21 17:49:45ID requested
12020-08-13 22:15:45announced
22020-09-25 03:01:09announced2020-09-25: Updated publication reference for PubMed record(s): 32965059.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: cancer mutations, human colon organoids, PORCN inhibitors, RNF 43, Wnt signaling, LC-MS/MS
Contact List
Zbynek Zdrahal
contact affiliationCEITEC—Central European Institute of Technology, Masaryk University, Brno, Czech Republic
contact emailzdrahal@sci.muni.cz
lab head
Katerina Hanakova
contact affiliationCEITEC MU
contact emailkaterina.hanak@gmail.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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