Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/60365
標題: Sumoylation of LAP1 is involved in the HDAC4-mediated repression of COX-2 transcription
作者: Wang, W.L.
楊文明
Lee, Y.C.
Yang, W.M.
Chang, W.C.
Wang, J.M.
關鍵字: ccaat/enhancer-binding proteins
cyclooxygenase-2 promoter activity
c/ebp-beta isoforms
gene-expression
histone deacetylases
c-jun
inflammatory mediators
messenger-rna
activation
macrophages
期刊/報告no:: Nucleic Acids Research, Volume 36, Issue 19, Page(s) 6066-6079.
摘要: CEBPB, one of the CEBP family members, is a crucial regulator of gene expression during innate immunity, inflammatory responses and adipogenesis. In this study, the EGF-induced increase of CEBPB mRNA is shown to be coincident with the decrease of COX-2 mRNA. We identified that all of the individual CEBPB isoforms, LAP1, LAP2 and LIP, attenuate EGF-induced COX-2 promoter activity. Although increased sumoylation of both LAP1 and LAP2 is observed during the lagging stage of EGF treatment, only the sumoylated LAP1, but not the sumoylated LAP2, is responsible for COX-2 gene repression. In addition, EGF treatment can regulate the nucleocytoplasmic redistribution of HDAC4 and SUMO1. We further demonstrated by loss-of- and gain-of-function approaches that HDAC4 can be a negative regulator while inactivating COX-2 transcription. The sumoylation mutant LAP1, LAP1K174A, exhibits an attenuated ability to interact with HDAC4, and increased COX-2 promoter activity. Furthermore, the in vivo DNA binding assay demonstrated that LAP1K174A and CEBPDK120A, sumoylation-defective CEBPD mutants, attenuate the binding of HDAC4 on the COX-2 promoter. In light of the above, our data suggest that the suCEBPD and suLAP1 are involved in the repression of COX-2 transcription through the recruitment of HDAC4.
URI: http://hdl.handle.net/11455/60365
ISSN: 0305-1048
文章連結: http://dx.doi.org/10.1093/nar/gkn607
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