Reference - Detail
|Author||Kawasaki H, Komai K, Nakamura M, Yamamoto E, Ouyang Z, Nakashima T, Morisawa T, Hashiramoto A, Shiozawa K, Ishikawa H, Kurosaka M, Shiozawa S.|
|Title||Human wee1 kinase is directly transactivated by and increased in association with c-Fos/AP-1: rheumatoid synovial cells overexpressing these genes go into aberrant mitosis.|
Wee1 kinase downregulates the M-phase promoting factor, a complex of cdc2 and cyclin B kinase, that controls mitotic cell division. We isolated human wee1 kinase gene promoter and found that it contained one AP-1-binding motif in its promoter region (5'-CGAGTCA-3'; -823/-817), through which wee1 kinase gene was directly transactivated by c-Fos/AP-1. In rheumatoid synovial cells, wee1 kinase was increased in conjunction with the increase of c-Fos/AP-1 and the substrate of wee1, cdc2, was phosphorylated. The amount of wee1 and c-Fos and the phosphorylation of cdc2 were decreased after treatment of the cells with an inhibitor of AP-1, curcumin. A significant proportion of cultured synovial cells of the patients with rheumatoid arthritis, but not those of osteoarthritis, shifted to a tetraploid (4C) state upon long-term culture. Thus, human wee1 kinase gene is directly transactivated by and increased in association with c-Fos/AP-1, and rheumatoid synovial cells overexpressing these genes go into aberrant mitosis.
|MeSH||Aged Amino Acid Motifs Arthritis, Rheumatoid / genetics* Arthritis, Rheumatoid / pathology CDC2 Protein Kinase / drug effects CDC2 Protein Kinase / metabolism Cell Cycle Proteins* Cells, Cultured Curcumin / pharmacology Enzyme Inhibitors / pharmacology Gene Expression Regulation, Enzymologic HeLa Cells Humans Middle Aged Mitosis / physiology Molecular Sequence Data Nuclear Proteins / genetics Nuclear Proteins / metabolism* Phosphorylation Ploidies Promoter Regions, Genetic Protein-Tyrosine Kinases / drug effects Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism* Proto-Oncogene Proteins c-fos / drug effects Proto-Oncogene Proteins c-fos / genetics Proto-Oncogene Proteins c-fos / metabolism* Substrate Specificity Synovial Membrane / pathology Transcription Factor AP-1 / chemistry Transcription Factor AP-1 / drug effects Transcription Factor AP-1 / metabolism* Transcriptional Activation*|
|WOS Category||GENETICS & HEREDITY ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|
|Human and Animal Cells|