title: Distinct domains of human CDC5 direct its nuclear import and association with the spliceosome.
abstract: Genetic studies have shown that CDC5 proteins are essential for G2 progression and mitotic entry. CDC5 homologs in yeast and mammals are essential for pre-messenger ribonucleic acid (mRNA) processing. Other gene products also have been shown to play roles in both pre-mRNA splicing and cell cycle regulation, prompting the description of several models to explain the mechanism(s) linking these two processes. In this study, we demonstrate that the amino-terminus of human CDC5 directs nuclear import independent of consensus nuclear localization signals or phosphorylation, and that the carboxyl-terminus of human CDC5 preferentially associates with spliceosomal complexes in proximity of RNA transcription during interphase. hCDC5 colocalizes with Sm proteins in a cell cycle- and domain-dependent manner, and several proteins in the human CDC5-associated complex are identified that suggest potential roles for the complex in coupling pre-mRNA splicing to transcriptional activation and protein translation. These results indicate that human CDC5 may function in pre-mRNA processing and cell cycle progression through more than one mechanism.
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001324:Autoantigens; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D016195:G2 Phase / Q000502:physiology; D006801:Humans; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000502:physiology; D019913:Nuclear Localization Signals / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D012326:RNA Splicing / Q000502:physiology*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism*; D055517:snRNP Core Proteins
chemical_list: D001324:Autoantigens; D018797:Cell Cycle Proteins; D019913:Nuclear Localization Signals; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins