Dissociation of bone morphogenetic protein-mediated growth arrest and apoptosis of mouse B cells by HPV-16 E6/E7

Kenji Yamato, Shinichi Hashimoto, Nobuo Okahashi, Akira Ishisaki, Koji Nonaka, Takeyoshi Koseki, Masahiro Kizaki, Yasuo Ikeda, Tatsuji Nishihara

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

We have previously found that bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor-β family, induces cell-cycle arrest in the G1 phase and apoptotic cell death of HS-72 mouse hybridoma cells. In this study, we show that BMP-2 did not alter expression of cyclin D, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4, p27(KIP1) p16(INK4a), or p15(INK1b), but enhanced expression of p21(CIP1/WAF1). Accumulation of p21(CIP1/WAF1) resulted in increased binding of p21(CIP1/WAF1) to CDK4 and concomitantly caused a profound decrease in the in vitro retinoblastoma protein (Rb) kinase activity of CDK4. Furthermore, the ectopic expression of human papilloma virus type-16 E7, an inhibitor of p21(CIP1/waf1) and Rb, reverted G1 arrest induced by BMP-2. Expression of E6/E7, without increasing the p53 level, blocked inhibition of Rb phosphorylation and G1 arrest, but did not attenuate cell death in BMP-treated HS-72 cells. Taken together, these results suggest that inhibition of Rb phosphorylation by p21(CIP1/WAF1) is responsible for BMP-2-mediated G1 arrest and that BMP-2-induction of apoptosis might be independent of Rb hypophosphorylation. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)198-205
Number of pages8
JournalExperimental Cell Research
Volume257
Issue number1
DOIs
Publication statusPublished - 2000 May 25
Externally publishedYes

Keywords

  • Apoptosis
  • BMP
  • E6/E7
  • G1 arrest
  • HPV-16 E7
  • P21(CIP1/WAF1)

ASJC Scopus subject areas

  • Cell Biology

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