Beta-catenin recruits CDC73 and LEO1

Stable Identifier
R-HSA-3322424
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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The C-terminal region of beta-catenin (ARM repeat 12 through the C-terminal domain) interacts directly with CDC73/Parafibromin, a component of the PAF1 complex (Mosimann et al, 2006). PAF1 is a conserved protein complex that affects aspects of RNA polymerase II transcription including histone modification, transcription elongation and RNA 3' end formation, among others (reviewed in Tomson and Arndt, 2013). In humans, the PAF1 complex consists of CDC73, PAF1, LEO1, CTR9, RTF1 and WDR61. Endogenous beta-catenin from HEK293 and HeLa cells can be co-immunoprecipitated with either CDC73 or LEO1, suggesting that the whole PAF1 complex may be associated with beta-catenin in vivo (Mosimann et al, 2006). The interaction between beta-catenin and CDC73 may be regulated by SHP2-mediated dephosphorylation of CDC73 (Takahashi et al, 2011). Overexpression of CDC73 stimulates expression of a WNT-responsive reporter in HEK293 cells; this enhancement is abrogated when hPYGO2 is depleted or the interaction between beta-catenin and BCL9 is disrupted. These results, which suggest that BCL9-PYGO may act in parallel to CDC73, are supported by the observation that CDC73 and beta-catenin coprecipitate with BCL9 and PYGO2 in HEK293 cells (Mosimann et al, 2006). CDC73 is frequently mutated in parathyroid carcinomas, and these tumors demonstrate aberrant WNT signaling (Juhlin et al, 2009).

Literature References
PubMed ID Title Journal Year
22982193 The many roles of the conserved eukaryotic Paf1 complex in regulating transcription, histone modifications, and disease states

Tomson, BN, Arndt, KM

Biochim. Biophys. Acta 2013
19148484 Loss of expression for the Wnt pathway components adenomatous polyposis coli and glycogen synthase kinase 3-beta in parathyroid carcinomas

Juhlin, CC, Haglund, F, Villablanca, A, Forsberg, L, Sandelin, K, Bränström, R, Larsson, C, Höög, A

Int. J. Oncol. 2009
21726809 SHP2 tyrosine phosphatase converts parafibromin/Cdc73 from a tumor suppressor to an oncogenic driver

Takahashi, A, Tsutsumi, R, Kikuchi, I, Obuse, C, Saito, Y, Seidi, A, Karisch, R, Fernandez, M, Cho, T, Ohnishi, N, Rozenblatt-Rosen, O, Meyerson, M, Neel, BG, Hatakeyama, M

Mol. Cell 2011
16630820 Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo

Mosimann, C, Hausmann, G, Basler, K

Cell 2006
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