title: p53-independent expression of p21(CIP1/WAF1) in plasmacytic cells during G(2) cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin.
abstract: The cytolethal distending toxin (CDT) from Actinobacillus actinomycetemcomitans has been shown to induce cell cycle arrest in the G(2)/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 G(2) cell cycle arrest in HS-72 cells and that rCDT upregulated expression of the cyclin-dependent kinase inhibitor p21(CIP1/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 p21(CIP1/WAF1) or G(2) cell cycle arrest upon exposure to rCDT. Furthermore, ectopic expression of a dominant negative p53 mutant did not inhibit rCDT-mediated p21(CIP1/WAF1) expression or G(2) cell cycle arrest in HS-72 cells. These results suggest that the CDT from A. actinomycetemcomitans induces p21(CIP1/WAF1) expression and G(2) 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 G(2) cell cycle arrest and that an increased level of p21(CIP1/WAF1) may be important for sustaining G(2) cell cycle arrest in several mammalian cells.
authors.affiliation: Department of Oral Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sato
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Koseki
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamato
authors.forename: Keitarou
authors.initials: K
authors.lastname: Saiki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Konishi
authors.forename: Masanosuke
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Isao
authors.initials: I
authors.lastname: Ishikawa
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Nishihara
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans; D000818:Animals; D001402:B-Lymphocytes; D001427:Bacterial Toxins / Q000235:genetics / Q000494:pharmacology*; D019556:COS Cells; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002522:Chlorocebus aethiops; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D016195:G2 Phase / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D001427:Bacterial Toxins; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; C447141:cytolethal distending toxin, Actinobacillus actinomycetemcomitans