ArticleCell cycle (Georgetown, Tex.)2008
Cell cycle-dependent phosphorylation of human CDC5 regulates RNA processing.
Article in Cell cycle (Georgetown, Tex.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- CDC5L binds to ELAVL1 to inhibit pyroptosis in hepatocellular carcinoma through the Caspase 3/GSDME signaling pathway.International journal of molecular medicine · 2025Article
- The emerging significance of splicing in vertebrate development.Development (Cambridge, England) · 2022Review
- DNA and RNA Binding Proteins: From Motifs to Roles in Cancer.International journal of molecular sciences · 2022Review
- CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5 is an RNA-binding protein controlling plant immunity via an RNA processing complex.The Plant cell · 2022Article
- Depletion of CDC5L inhibits bladder cancer tumorigenesis.Journal of Cancer · 2020Article
- Evidence for a Strong Correlation Between Transcription Factor Protein Disorder and Organismic Complexity.Genome biology and evolution · 2017Article
- Differential DNA methylation and PMEpigenetics · 2017Article
- Small angle X-ray scattering studies of CTNNBL1 dimerization and CTNNBL1/CDC5L complex.Scientific reports · 2015Article
- Phosphoproteomic analysis of the highly-metastatic hepatocellular carcinoma cell line, MHCC97-H.International journal of molecular sciences · 2015Article
- The spliceosome-activating complex: molecular mechanisms underlying the function of a pleiotropic regulator.Frontiers in plant science · 2012Article
- Semiquantitative proteomic analysis of the human spliceosome via a novel two-dimensional gel electrophoresis method.Molecular and cellular biology · 2011Article
- Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis.RNA (New York, N.Y.) · 2010Article
- Molecular architecture of the human Prp19/CDC5L complex.Molecular and cellular biology · 2010Article
- Identification of CDK2 substrates in human cell lysates.Genome biology · 2008Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.