title: Mouse Wee1 gene is repressed by Krüppel-like factor 3 (KLF3) via interaction with multiple upstream elements.
abstract: Wee1 protein kinase represses CDK1 required for G(2)/M transition. The mouse wee1 promoter contains multiple CACCC-boxes between -306 and +1 that can bind to Krüppel-like factor 3 (KLF3) transcriptional repressor. We found that increasing amounts of intracellular KLF3 decreased the amount of wee1 mRNA. A promoter reporter assay demonstrated that wee1 promoter activity was repressed by KLF3 overexpression. Elimination of the first and fourth CACCC-boxes suppressed KLF3-governed transcriptional repression. A gel-shift assay demonstrated that KLF3 binds to the first, third, and fourth CACCC-boxes with various strengths. Moreover, KLF3 was suggested to interact with the wee1 regulatory region in a physiological condition. Therefore, we concluded that KLF3 is a transcriptional repressor for wee1 gene. In a previous study, we demonstrated that TBP-like protein (TLP) inhibits wee1 promoter function. In this study, we found that the chromosomal wee1 gene is also down-regulated by KLF3. Since KLF3-repressed wee1 promoter function was further inhibited by TLP overexpression regardless of the inhibition degree of KLF3, we propose that TLP and KLF3 repress wee1 promoter independently.
authors: Graduate School of Science, Chiba University, 1–33 Yayoicho, Chiba 263–8522, Japan.
authors: Takuya
authors: T
authors: Kitamura
authors: Hidefumi
authors: H
authors: Suzuki
authors: Taka-aki
authors: TA
authors: Tamura
mesh_terms: D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional
chemical_list: D018797:Cell Cycle Proteins; C529780:Klf3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; C499348:Wee1 protein, mouse