Transcriptional regulation of angiogenesis-related puromycin-insensitive leucyl-specific aminopeptidase in endothelial cells.
Puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) was expressed in endothelial cells (ECs) and played an important role in angiogenesis. Here, we characterized its transcriptional regulation. Mouse PILSAP gene contained 19 exons and located in the chromosome 13C1-C2. We identified two transcripts; one transcribed from exon 1 and the other from exon 2. Mouse ECs expressed dominantly the one from exon 1. The promoter analysis using 5' upstream region of exon 1 revealed that -1868 to -1812 was critical for its transcription in mouse ECs. We identified a motif of the transcription factor PEBP2 in this region, and the deletion or mutation of this motif decreased promoter activity. Protein extracted from mouse ECs bound specifically to this motif. AML1/Runx1/PEBP2alphaB increased PILSAP mRNA in mouse ECs, whereas dominant interfering chimerical PEBP2beta-MYH11 decreased it. These results indicate that the expression of PILSAP in mouse ECs is regulated, at least in part, by PEBP2.
Niizeki
Osamu
O
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Miyashita
Hiroki
H
Yamazaki
Tohru
T
Akada
Tetsuya
T
Abe
Mayumi
M
Yoshida
Naomi
N
Watanabe
Toshio
T
Yoshimatsu
Hironobu
H
Sato
Yasufumi
Y
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002875:Chromosomes / Q000235:genetics / Q000648:ultrastructure; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D005091:Exons / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D007438:Introns / Q000235:genetics; D007931:Leucyl Aminopeptidase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection
D014157:Transcription Factors; D008156:Luciferases; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase