Calcineurin-induced apoptosis and TMD

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18592029
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Osaka University
• Principal Investigator: SAEKI Makio Osaka University, Graduate School of Dentistry, Pharmacology, Assistant Professor (30273692)
• Co-Investigator(Kenkyū-buntansha): KAMISAKI Yoshinori Osaka University, Graduate School of Dentistry Pharmacology, Professor (40116017)
• Project Period (FY): 2006 – 2007
• Keywords: apoptosis / calcineurin / caspase / cell death

Research Abstract

Overexpression of calcineurin B in HEK 293 cells potentiated processing of caspase-3 and apoptosis triggered by tumor necrosis factor-α and cycloheximide treatment. In a cell-free system, overexpression of calcineurin B in HEK 293 cells markedly increased processing of caspase-3 by cytochrome c. Immunodepletion of calcineurin B from cytosolic extracts from Jurkat cells decreased processing of caspase-3 by cytochrome c. Knockdown of calcineurin B by RNA interference resulted in a reduced apoptosis in HEK293 cells, but not in caspase-3-deficient MCF-7 cells. These results suggest that calcineurin B may possess a novel function to participate in the regulation of apoptosis, in addition to its well-known ability to regulate calcineurin A. Furthermore, calcineurin B itself has no effect on apoptosis, but promotes apoptotic signal transduction system through the presentation of scaffold for the activation of caspase-3 by caspase-9. Therefore, calcineurin B may be useful for therapies to induce and promote apoptosis.

Research Products

• [Journal Article] Calcineurin Potentiates the Activation of Procaspase-3 by Accelerating Its Proteolytic Maturation (2007)
  • Author(s): Saeki M, Irie Y, Ni L, Itsuki Y, Terao Y, Kawabata S and Kamisaki Y
  • Journal Title: The Journal of Biological Chemistry 282 Pages: 11786-11794
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Calcineurin Potentiates the Activation of Procaspase-3 by Accelerating Its Proteolytic Maturation (2007)
  • Author(s): Saeki, M, Irie, Y, Ni, L, Itsuki, Y, Terao, Y, Kawabata, S, Kamisaki, Y
  • Journal Title: The Journal of Biological Chemistry 282 Pages: 11786-11794
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Monad, a WD40 repeat protein, promotes apoptosis induced by TNF-α (2006)
  • Author(s): Saeki M, Irie Y, Ni L, Yoshida M, Itsuki Y and Kamisaki Y
  • Journal Title: Biochemical and Biophysical Reseazch Communications 342 Pages: 568-572
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] a WD40 repeat protein, promotes apoptosis induced by TNF-a (2006)
  • Author(s): Saeki, M, Irie, Y, Ni, L, Yoshida, M, Itsuki, Y, Kamisaki, Y, Monad
  • Journal Title: Biochemical and Biophysical Research Communications 342 Pages: 568-572
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://www.dent.osaka-u.ac.jp/~pharm/index.html