Cell cycle-dependent phosphorylation of human CDC5 regulates RNA processing
| العنوان: | Cell cycle-dependent phosphorylation of human CDC5 regulates RNA processing |
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| المؤلفون: | Meihua Chu, Remo Gräub, Xiao-Qin Xu, David Stokoe, Hope Lancero, Harold S. Bernstein, Paul Spitz, Krishnan Padmanabhan, Robert J. Chalkley, Alma L. Burlingame, Anissa Pedersen |
| المصدر: | Cell Cycle. 7:1795-1803 |
| بيانات النشر: | Informa UK Limited, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Spliceosome, Cell Cycle Proteins, Biology, Peptide Mapping, Article, Phosphorylation cascade, Cyclin-dependent kinase, Chlorocebus aethiops, Animals, Humans, Protein phosphorylation, Enzyme Inhibitors, Phosphorylation, RNA Processing, Post-Transcriptional, Molecular Biology, Cell Nucleus, Kinase, Cell Cycle, Cyclin-dependent kinase 2, RNA-Binding Proteins, Cell Biology, Cell biology, enzymes and coenzymes (carbohydrates), Biochemistry, Purines, COS Cells, RNA splicing, biology.protein, Dimerization, Developmental Biology |
| الوصف: | CDC5 proteins are components of the pre-mRNA splicing complex and essential for cell cycle progression in yeast, plants and mammals. Human CDC5 is phosphorylated in a mitogen-dependent manner, and its association with the spliceosome is ATP-dependent. Examination of the amino acid sequence suggests that CDC5L may be phosphorylated at up to 28 potential consensus recognition sequences for known kinases, however, the identity of actual phosphorylation sites, their role in regulating CDC5L activity, and the kinases responsible for their phosphorylation have not previously been determined. Using two-dimensional phosphopeptide mapping and nanoelectrospray mass spectrometry, we now show that CDC5L is phosphorylated on at least nine sites in vivo. We demonstrate that while CDC5L is capable of forming homodimers in vitro and in vivo, neither homodimerization nor nuclear localization is dependent on phosphorylation at these sites. Using an in vitro splicing assay, we show that phosphorylation of CDC5L at threonines 411 and 438 within recognition sequences for CDKs are required for CDC5L-mediated pre-mRNA splicing. We also demonstrate that a specific inhibitor of CDK2, CVT-313, inhibits CDC5L phosphorylation in both in vitro kinase assays and in vivo radiolabeling experiments in cycling cells. These studies represent the first demonstration of a regulatory role for phosphorylation of CDC5L, and suggest that targeting these sites or the implicated kinases may provide novel strategies for treating disorders of unguarded cellular proliferation, such as cancer. |
| تدمد: | 1551-4005 1538-4101 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c77483b861ac8d41f85fe1bccbe40073 https://doi.org/10.4161/cc.7.12.6017 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c77483b861ac8d41f85fe1bccbe40073 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 15514005 15384101 |
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