RRC ID 41992
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.
Journal Oncogene
Abstract 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.
Volume 22(44)
Pages 6839-44
Published 2003-10-9
DOI 10.1038/sj.onc.1206903
PII 1206903
PMID 14534529
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*
IF 6.634
Times Cited 21
WOS Category GENETICS & HEREDITY ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Human and Animal Cells