The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression

A. Inoue, Masashi Yanagisawa, Y. Takuwa, Y. Mitsui, M. Kobayashi, T. Masaki

Research output: Contribution to journalArticle

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Abstract

Endothelin-1 is a 21-amino acid potent vasoconstrictor peptide produced by vascular endothelial cells. We have cloned the whole length of the human preproendothelin-1 (PPET-1) gene and the corresponding cDNA and determined the complete nucleotide sequences. The 2026-nucleotide human mRNA for PPET-1 (excluding the poly(A) tail) is encoded in five exons distributed over 6836 base pairs of the genome. The 5'-flanking region of the gene contains (i) octanucleotide sequences for the phorbol ester-responsive elements, also known as the binding elements for FOS · JUN complex; (ii) consensus motifs for the binding site of nuclear factor 1, which may mediate the induction described previously of PPET-1 mRNA by transforming growth factor-β; (iii) hexanucleotide sequences for the acute phase reactant regulatory elements that may be involved in the induction of endothelin-1 under acute physical stress in vivo. Further, the 3'-nontranslated sequence of human PPET-1 mRNA contains three AUUUA motifs, which may mediate selective translation-dependent destabilization of the mRNA. Northern blot analysis in cultured endothelial cells from human umbilical veins shows that PPET-1 mRNA is in fact rapidly induced by the active phorbol ester 12-O-tetradecanoylphorbol 13-acetate within 10 min. Analysis of mRNA life span by using actinomycin D demonstrates that PPET-1 mRNA has a short intracellular half-life of about 15 min and is superinduced by cycloheximide. This superinduction is found to be due to the stabilization of the mRNA by cycloheximide, as in the case of other known AUUUA-containing mRNAs. These findings suggest that the regulation of expression of PPET-1 mRNA may be mediated in part by these sequence elements.

Original languageEnglish (US)
Pages (from-to)14954-14959
Number of pages6
JournalJournal of Biological Chemistry
Volume264
Issue number25
StatePublished - 1989

Fingerprint

Endothelin-1
Nucleotides
Genes
Messenger RNA
Endothelial cells
Phorbol Esters
Cycloheximide
Endothelial Cells
NFI Transcription Factors
Umbilical Veins
Acute-Phase Proteins
5' Flanking Region
Transforming Growth Factors
Dactinomycin
Vasoconstrictor Agents
Tetradecanoylphorbol Acetate
2-(2-(1-phenyl-4-piperazynyl)ethyl)-1,2,3,4-tetrahydro-beta-carboline-1-spiro-4'-N'-benzylpiperidine
Base Pairing
Northern Blotting
Half-Life

ASJC Scopus subject areas

  • Biochemistry

Cite this

Inoue, A., Yanagisawa, M., Takuwa, Y., Mitsui, Y., Kobayashi, M., & Masaki, T. (1989). The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression. Journal of Biological Chemistry, 264(25), 14954-14959.

The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression. / Inoue, A.; Yanagisawa, Masashi; Takuwa, Y.; Mitsui, Y.; Kobayashi, M.; Masaki, T.

In: Journal of Biological Chemistry, Vol. 264, No. 25, 1989, p. 14954-14959.

Research output: Contribution to journalArticle

Inoue, A, Yanagisawa, M, Takuwa, Y, Mitsui, Y, Kobayashi, M & Masaki, T 1989, 'The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression', Journal of Biological Chemistry, vol. 264, no. 25, pp. 14954-14959.
Inoue, A. ; Yanagisawa, Masashi ; Takuwa, Y. ; Mitsui, Y. ; Kobayashi, M. ; Masaki, T. / The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression. In: Journal of Biological Chemistry. 1989 ; Vol. 264, No. 25. pp. 14954-14959.
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