Role of BI-1 (TEGT)-mediated ERK1/2 activation in mitochondria-mediated apoptosis and splenomegaly in BI-1 transgenic mice

Jung Hyun Kim, Eung Ryoung Lee, Kilsoo Jeon, Hye Yeon Choi, Hyejin Lim, Su Jeong Kim, Han Jung Chae, Seung Hwa Park, Sang Uk Kim, Young Rok Seo, Jin Hoi Kim, Ssang Goo Cho

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Bax Inhibitor-1 (BI-1) is an evolutionally conserved apoptotic suppressor and belongs to the BI-1 family of proteins, which contain BI-1-like transmembrane domains. As their cellular functions and regulatory mechanisms remain incompletely understood, we compared their anti-apoptotic properties. Forced expression of BI-1 resulted in the most effective suppression of stress-induced apoptosis, compared with other family members, together with significant extracellular signal-regulated kinase (ERK)1/2 activation. BI-1-mediated ERK1/2 activation led to the suppression of mitochondria-mediated reactive oxygen species (ROS) production. Involvement of the ERK signaling pathway in BI-1-induced anti-apoptotic effects was confirmed by knockdown studies with ERK- or BI-1-specific siRNA. Moreover, we produced transgenic (TG) mice overexpressing BI-1, and the relationship between ERK1/2 activation and the suppression of ROS production or apoptosis was confirmed in mouse embryonic fibroblast (MEF) cells derived from these mice. Interestingly, we found that BI-1 TG mice showed splenomegaly and abnormal megakaryopoiesis. Taken together, our results suggest that BI-1-induced ERK1/2 activation plays an important role in the modulation of intracellular ROS generation and apoptotic cell death and may also affect autoimmune response.

Original languageEnglish
Pages (from-to)876-888
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1823
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Autoimmune response
  • Bax inhibitor-1
  • BI-1 family protein
  • ERK1/2
  • Splenomegaly

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