c-Fos/activator protein-1 transactivates wee1 kinase at G(1)/S to inhibit premature mitosis in antigen-specific Th1 cells.
M-phase promoting factor is a complex of cdc2 and cyclin B that is regulated positively by cdc25 phosphatase and negatively by wee1 kinase. We isolated the wee1 gene promoter and found that it contains one AP-1 binding motif and is directly activated by the immediate early gene product c-Fos at cellular G(1)/S phase. In antigen-specific Th1 cells stimulated by antigen, transactivation of the c-fos and wee1 kinase genes occurred sequentially at G(1)/S, and the substrate of wee1 kinase, cdc2-Tyr15, was subsequently phosphorylated at late G(1)/S. Under prolonged expression of the c-fos gene, however, the amount of wee1 kinase was increased and its target cdc2 molecule was constitutively phosphorylated on its tyrosine residue, where Th1 cells went into aberrant mitosis. Thus, an immediate early gene product, c-Fos/AP-1, directly transactivates the wee1 kinase gene at G(1)/S. The transient increase in c-fos and wee1 kinase genes is likely to be responsible for preventing premature mitosis while the cells remain in the G(1)/S phase of the cell cycle.
Kawasaki
H
H
Division of Clinical Immunology, Faculty of Health Science, Kobe University School of Medicine, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142, Japan.
Komai
K
K
Ouyang
Z
Z
Murata
M
M
Hikasa
M
M
Ohgiri
M
M
Shiozawa
S
S
D000818:Animals; D000941:Antigens / Q000276:immunology; D001665:Binding Sites; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D016193:G1 Phase; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D018417:Th1 Cells / Q000166:cytology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation
D000941:Antigens; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D011505:Protein-Tyrosine Kinases; C499348:Wee1 protein, mouse