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CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation.

J. Biol. Chem.. 2015-05; 
PisanoAntonio,CegliaSimona,PalmieriCamillo,VecchioEleonora,FiumeGiuseppe,de LaurentiisAnnamaria,MimmiSelena,FalconeCristina,IaccinoEnrico,ScialdoneAnnarita,PontorieroMarilena,MasciFrancesca Fasanella,ValeaRosanna,KrishnanShibu,GaspariMarco,CudaGiovanni,ScalaGiuseppe,QuintoIl
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Custom Vector Construction … The prokaryotic expression vector of Pdcd4 wild type and mutants fused to GST (GST-Pdcd4-WT, GST-Pdcd4DRBD, or GST-Pdcd4RBDStop) were a kind gift of Dr. KH Klempnauer (Westfalische-Wilhelms-Universitat Munster). GenScript Corp … Get A Quote

摘要

The human inhibitor of Bruton's tyrosine kinase isoform α (IBtkα) is a BTB protein encoded by the IBTK gene, which maps to chromosomal locus 6q14.1, a mutational hot spot in lymphoproliferative disorders. Here, we demonstrate that IBtkα forms a CRL3(IBTK) complex promoting its self-ubiquitylation. We identified the tumor suppressor Pdcd4 as IBtkα interactor and ubiquitylation substrate of CRL3(IBTK) for proteasomal degradation. Serum-induced degradation of Pdcd4 required both IBtkα and Cul3, indicating that CRL3(IBTK) regulated the Pdcd4 stability in serum signaling. By promoting Pdcd4 degradation, IBtkα counteracted the suppressive effect of Pdcd4 on translation of reporter luciferase mRNAs wit... More

关键词

E3 ubiquitin ligase,IBtk,Pdcd4,serum,translation regulation,tumor suppressor gene,ubiquitylation (ubiquitinat