Open AccessRegulation of Gadd45γ expression by C/EBP
Author(s) -
Jung Neoncheol,
Yi YongWeon,
Kim Daegun,
Shong Minho,
Hong SeungSuh,
Lee HyunSoo,
Bae Insoo
Publication year - 2000
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.2000.01692.x
Subject(s) - ccaat enhancer binding proteins , microbiology and biotechnology , electrophoretic mobility shift assay , biology , gadd45 , transcription factor , promoter , transcription (linguistics) , gene expression , enhancer , gene , regulation of gene expression , reporter gene , nuclear protein , cell cycle , cell cycle checkpoint , genetics , linguistics , philosophy
The Gadd45γ (growth arrest and DNA damage‐inducible) gene is activated transcriptionally by at least two kinds of agents: DNA damaging agent such as methyl methanesulfonate (MMS) and UV radiation, or cytokines such as interleukin (IL)‐6, IL‐2 and granulocyte colony‐stimulating factor (G‐CSF). To investigate the sequences and transcription factors involved in induction of Gadd45γ after treatment with IL‐6, the human gene was cloned and sequenced. We found C/EBP (CCAAT/enhancer‐binding protein) family proteins, major transcription factors in the IL‐6 signal transduction pathway, could regulate the transcriptional activity of the Gadd45γ promoter. In addition, a noncanonical C/EBP‐binding site within the Gadd45γ promoter where C/EBPβ and C/EBPδ could bind, was identified by electrophoretic mobility shift assay (EMSA) and reporter gene analysis. Furthermore, we found a coordinated expression profile between Gadd45γ mRNA and C/EBPs (β and δ) protein during the differentiation of M1 cells: the amount of Gadd45γ transcripts became maximal when both C/EBPβ and C/EBPδ levels were high, on day 1 of differentiation of M1 cells after treatment with IL‐6. These findings suggest that mitotic growth arrest coupled to M1 cell differentiation is mediated by C/EBPs stimulation of growth arrest‐associated genes such as Gadd45γ .