Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax

Sandy M. Cuddeback, Hirohito Yamaguchi, Kiyoshi Komatsu, Toshiyuki Miyashita, Masao Yamada, Chun Wu, Sujay Singh, Hong Gang Wang

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

Bax is a proapoptotic member of the Bcl-2 protein family that commits the cell to undergo programmed cell death in response to apoptotic stimuli. To gain further insights into Bax mechanisms, we have identified a novel Bax-binding protein, termed Bif-1, by using a yeast two-hybrid cloning technique. Bif-1 is an evolutionarily conserved cytoplasmic protein that contains a predicted Src homology 3 (SH3) domain located near its C terminus but shares no significant homology with members of the Bcl-2 family. A Northern blot analysis indicates that Bif-1 is expressed in most tissues with abundant expression in heart and skeletal muscle. Bif-1 is capable of interacting with Bax as demonstrated by yeast two-hybrid, coimmunoprecipitation, and immunofluorescence studies. Induction of apoptosis in murine pre-B hematopoietic cells FL5.12 by interleukin-3 withdrawal results in increased association of Bax with Bif-1, which is accompanied by a conformational change in the Bax protein. Overexpression of Bif-1 promotes Bax conformational change, caspase activation, and apoptotic cell death in FL5.12 cells following interleukin-3 deprivation. Bif-1 thus represents a new type of regulator of Bax-mediated signaling pathways for apoptosis.

Original languageEnglish (US)
Pages (from-to)20559-20565
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number23
DOIs
StatePublished - Jun 8 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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