Rac1-dependent transcriptional up-regulation of p27Kip1 by homophilic cell-cell contact in vascular endothelial cells

Mayumi Hirano, Hideo Kanaide, Katsuya Hirano

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The mechanism for the transcriptional up-regulation of p27Kip1 due to the formation of the cell-cell contact was investigated in vascular endothelial cells. The induction of the cell-cell contact by adding an extra number of endothelial cells activated Rac1, up-regulated p27Kip1 mRNA and protein, and also facilitated the cell cycle arrest. Transduction of the Rac1 inhibitor protein using the cell-penetrating peptide or treatment with a Rac1 inhibitor NSC23766 inhibited the p27Kip1 up-regulation and delayed the cell cycle arrest. Rac1 was therefore suggested to mediate the contact-induced transcriptional up-regulation of p27Kip1. The role of Rac1 in the regulation of the p27Kip1 promoter activity was next examined with a luciferase reporter assay. The promoter activity was increased by inducing the cell-cell contact, which was significantly inhibited by the Rac1 inhibitory protein and NSC23766. The evaluation of various truncated promoter regions determined region - 620 to - 573 nucleotides from the initiation codon to be responsible for the contact-induced, Rac1-dependent activation of the p27Kip1 promoter. The present study thus demonstrated for the first time that the activation of Rac1 due to the cell-cell contact plays a critical role in the transcriptional up-regulation of p27Kip1 in vascular endothelial cells.

Original languageEnglish
Pages (from-to)1500-1510
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1773
Issue number10
DOIs
Publication statusPublished - Oct 1 2007
Externally publishedYes

Fingerprint

Up-Regulation
Endothelial Cells
rac1 GTP-Binding Protein
Cell Cycle Checkpoints
Cell-Penetrating Peptides
Cyclin-Dependent Kinase Inhibitor p27
Initiator Codon
Luciferases
Genetic Promoter Regions
Nucleotides
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Molecular Biology
  • Biophysics

Cite this

Rac1-dependent transcriptional up-regulation of p27Kip1 by homophilic cell-cell contact in vascular endothelial cells. / Hirano, Mayumi; Kanaide, Hideo; Hirano, Katsuya.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1773, No. 10, 01.10.2007, p. 1500-1510.

Research output: Contribution to journalArticle

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