Protein kinase C-mediated inhibition of cyclin A expression in human vascular endothelial cells

Chiya Kosaka, Toshiyuki Sasaguri, Junichi Masuda, Katsuhiro Zen, Kentaro Shimokado, Tasuku Yokota, Jun Ogata

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Proliferation of cultured human vascular endothelial cells may be negatively regulated by the protein kinase C (PKC) pathway, because phorbol 12-myristate, 13-acetate (PMA) inhibits DNA synthesis and cell population doubling in PKC-retaining cells, but not in cells depleted of PKC by a long-term exposure to PMA. We investigated the mechanism through which PKC arrests the cell cycle with regard to cyclin A, which has been reported to play a key role in G1/S progression activating CDK2. Cyclin A mRNA was elevated from late G1 in accorance with the protein expression, which reached the maximal level during the S phase. PMA added at late G1 potently reduced the levels of cyclin A mRNA and the protein in concentration-dependent manners parallel to its effect on the proliferation. However, it failed to inhibit the expression in PKC-depleted cells. The mRNA reduction by PMA was due to inhibition of the transcription. The PMA effects were mimicked by multiple doses of 1,2-dioctanoylglycerol. These findings suggest that PKC inhibits G1/S progression through suppression of cyclcin A gene transcription in endothelial cells.

Original languageEnglish
Pages (from-to)991-998
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume193
Issue number3
DOIs
Publication statusPublished - Jun 30 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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