p53-independent expression of p21CIP1/WAF1 in plasmacytic cells during G2 cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin

Tsuyoshi Sato, Takeyoshi Koseki, Kenji Yamato, Keitarou Saiki, Kiyoshi Konishi, Masanosuke Yoshikawa, Isao Ishikawa, Tatsuji Nishihara

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50 Citations (Scopus)


The cytolethal distending toxin (CDT) from Actinobacillus actinomycetemcomitans has been shown to induce cell cycle arrest in the G2/M phase in HeLa cells. In the present study, the mechanism of CDT-induced cell cycle arrest was investigated by using HS-72 cells, a murine B-cell hybridoma cell line. Using flow cytometric analysis, we found that the recombinant CDT (rCDT) from A. actinomycetemcomitans induced G2 cell cycle arrest in HS-72 cells and that rCDT upregulated expression of the cyclin-dependent kinase inhibitor p21CIP1/WAF1 and the tumor suppressor protein p53. HS-72 cells transfected with the E6/E7 gene of human papillomavirus type 16, which lacked rCDT-induced accumulation of p53, exhibited expression of p21CIP1/WAF1 or G2 cell cycle arrest upon exposure to rCDT. Furthermore, ectopic expression of a dominant negative p53 mutant did not inhibit rCDT-mediated p21CIP1/WAF1 expression or G2 cell cycle arrest in HS-72 cells. These results suggest that the CDT from A. actinomycetemcomitans induces p21CIP1/WAF1 expression and G2 cell cycle arrest in B-lineage cells by p53-independent pathways. Together with additional observations made with HeLa cells and COS-1 cells cultured with the rCDT from A. actinomycetemcomitans, the results of this study indicate that CDT-induced p53 accumulation may not be required for G2 cell cycle arrest and that an increased level of p21CIP1/WAF1 may be important for sustaining G2 cell cycle arrest in several mammalian cells.

Original languageEnglish
Pages (from-to)528-534
Number of pages7
JournalInfection and immunity
Issue number2
Publication statusPublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases


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