CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation*
| العنوان: | CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation* |
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| المؤلفون: | Antonio Pisano, Shibu Krishnan, Giuseppe Scala, Marilena Pontoriero, Annarita Scialdone, Marco Gaspari, Francesca Fasanella Masci, Selena Mimmi, Annamaria de Laurentiis, Enrico Iaccino, Rosanna Valea, Giovanni Cuda, Camillo Palmieri, Cristina Falcone, Ileana Quinto, Eleonora Vecchio, Simona Ceglia, Giuseppe Fiume |
| المصدر: | The Journal of Biological Chemistry |
| بيانات النشر: | American Society for Biochemistry and Molecular Biology, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Gene isoform, Proteasome Endopeptidase Complex, Tumor suppressor gene, Ubiquitin-Protein Ligases, Amino Acid Motifs, Molecular Sequence Data, RNA-binding protein, translation regulation, Biochemistry, Mass Spectrometry, Mice, Ubiquitin, RNA interference, Sequence Homology, Nucleic Acid, Translational regulation, Animals, Homeostasis, Humans, ubiquitylation (ubiquitination), RNA, Messenger, tumor suppressor gene, RNA, Small Interfering, Molecular Biology, Psychological repression, Adaptor Proteins, Signal Transducing, biology, Base Sequence, Lentivirus, Intracellular Signaling Peptides and Proteins, RNA-Binding Proteins, Cell Biology, Molecular biology, IBtk, Glutathione, Ubiquitin ligase, Protein Structure, Tertiary, Pdcd4, HEK293 Cells, E3 ubiquitin ligase, Protein Synthesis and Degradation, biology.protein, RNA Interference, Apoptosis Regulatory Proteins, Carrier Proteins, serum, HeLa Cells, Protein Binding |
| الوصف: | Background: IBtkα is an uncharacterized protein belonging to the family of BTB proteins. Results: IBtkα is the substrate receptor for a Cullin3-dependent ubiquitin ligase promoting ubiquitylation and proteasomal degradation of Pdcd4. Conclusion: By regulating Pdcd4 stability, IBtkα can modulate the translation of specific mRNAs under different cellular conditions. Significance: The identification of new players in the ubiquitin/proteasome pathways contributes to a better understanding of protein homeostasis. 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 CRL3IBTK complex promoting its self-ubiquitylation. We identified the tumor suppressor Pdcd4 as IBtkα interactor and ubiquitylation substrate of CRL3IBTK for proteasomal degradation. Serum-induced degradation of Pdcd4 required both IBtkα and Cul3, indicating that CRL3IBTK regulated the Pdcd4 stability in serum signaling. By promoting Pdcd4 degradation, IBtkα counteracted the suppressive effect of Pdcd4 on translation of reporter luciferase mRNAs with stem-loop structured or unstructured 5′-UTR. IBtkα depletion by RNAi caused Pdcd4 accumulation and decreased the translation of Bcl-xL mRNA, a well known target of Pdcd4 repression. By characterizing CRL3IBTK as a novel ubiquitin ligase, this study provides new insights into regulatory mechanisms of cellular pathways, such as the Pdcd4-dependent translation of mRNAs. |
| اللغة: | English |
| تدمد: | 1083-351X 0021-9258 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::085c7e8fd7a90e19446c6e40e5a2fe35 http://europepmc.org/articles/PMC4447969 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....085c7e8fd7a90e19446c6e40e5a2fe35 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1083351X 00219258 |
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