Sumoylation of LAP1 is involved in the HDAC4-mediated repression of COX-2 transcription

Wen Ling Wang, Yi Chao Lee, Wen Ming Yang, Wen Chang Chang, Ju Ming Wang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6066-6079
Number of pages14
JournalNucleic Acids Research
Volume36
Issue number19
DOIs
Publication statusPublished - 2008
Externally publishedYes

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Sumoylation
Epidermal Growth Factor
Adipogenesis
Messenger RNA
Aptitude
Regulator Genes
Innate Immunity
Protein Isoforms
Gene Expression
DNA
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Sumoylation of LAP1 is involved in the HDAC4-mediated repression of COX-2 transcription. / Wang, Wen Ling; Lee, Yi Chao; Yang, Wen Ming; Chang, Wen Chang; Wang, Ju Ming.

In: Nucleic Acids Research, Vol. 36, No. 19, 2008, p. 6066-6079.

Research output: Contribution to journalArticle

Wang, Wen Ling ; Lee, Yi Chao ; Yang, Wen Ming ; Chang, Wen Chang ; Wang, Ju Ming. / Sumoylation of LAP1 is involved in the HDAC4-mediated repression of COX-2 transcription. In: Nucleic Acids Research. 2008 ; Vol. 36, No. 19. pp. 6066-6079.
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abstract = "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.",
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