SUMO down-regulates the activity of Elf4/myeloid Elf-1-like factor.
Myeloid elf-1-like factor (MEF) or Elf4 is an ETS protein known to regulate the basal expression of the anti-microbial peptides, lysozyme and human beta-defensin-2, in epithelial cells and activate the transcription of perforin in natural killer cells. The numerous target genes of MEF and its biological functions signify the importance of this Ets transcription factor. Here we show that MEF is modified by conjugation with SUMO-1/-2 (small ubiquitin-related modifier) both in mammalian cells and in Escherichia coli overexpressing human SUMO-1/-2. We identified by point mutation that lysine 657 of MEF is the site for sumoylation. This modification down-regulated MEF activity on lysozyme and perforin promoters, and decreased the lysozyme mRNA expression. Chromatin immuno-precipitation analysis revealed that SUMO-conjugation diminished the recruitment of MEF to the lysozyme promoter, which partly explains the down-regulation of MEF activity by SUMO. These findings contribute to our understanding of the regulation of the ETS factor MEF.
Suico
Mary Ann
MA
Department of Molecular Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Nakamura
Hideaki
H
Lu
Zhuo
Z
Saitoh
Hisato
H
Shuto
Tsuyoshi
T
Nakao
Mitsuyoshi
M
Kai
Hirofumi
H
D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D025842:SUMO-1 Protein / Q000378:metabolism / Q000502:physiology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C111931:ELF4 protein, human; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D001120:Arginine; D008239:Lysine