Hierarchical order of phosphorylation events commits Cdc25A to Beta-TrCP-dependent degradation

Transforming Growth Factor Facilitates -TrCP-Mediated Degradation of Cdc25A in a Smad3-Dependent Manner

Beta-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases.

Beta-TrCP, the F-box protein of the SCF(beta-TrCP) ubiquitin ligase (SCF, Skp1/Cul1/F-box protein), recognizes the doubly phosphorylated DSG motif (DpSGPhiXpS) in various SCF(beta-TrCP) target proteins. The Cdc25A phosphatase, a key cell-cycle regulator in vertebrate cells, undergoes a rapid ubiquitin-dependent degradation in response to genotoxic stress. Beta-TrCP binds to the DSG motif of hum...

S6K1 phosphorylation-dependent degradation of Mxi1 by β-Trcp ubiquitin ligase promotes Myc activation and radioresistance in lung cancer

Rationale: Mxi1 is regarded as a potential tumor suppressor protein that antagonizes the transcriptional activity of proto-oncogene Myc. However, the clinical significances and underlying mechanisms by which Mxi1 is regulated in lung cancer remain poorly understood. Methods: Mass spectrometry analysis and immunoprecipitation assay were utilized to detect the protein-protein interaction. The pho...

b-Trcp couples b-catenin phosphorylation-degradation and regulates Xenopus axis formation

Regulation of b-catenin stability is essential for Wnt signal transduction during development and tumorigenesis. It is well known that serine-phosphorylation of b-catenin by the Axin–glycogen synthase kinase (GSK)–3b complex targets b-catenin for ubiquitination–degradation, and mutations at critical phosphoserine residues stabilize b-catenin and cause human cancers. How b-catenin phosphorylatio...

beta-Trcp mediates ubiquitination and degradation of the erythropoietin receptor and controls cell proliferation.

Control of intensity and duration of erythropoietin (Epo) signaling is necessary to tightly regulate red blood cell production. We have recently shown that the ubiquitin/proteasome system plays a major role in the control of Epo-R signaling. Indeed, after Epo stimulation, Epo-R is ubiquitinated and its intracellular part is degraded by the proteasome, preventing further signal transduction. The...