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 language | English (US) |
|---|---|
| Pages (from-to) | 20559-20565 |
| Number of pages | 7 |
| Journal | Journal of Biological Chemistry |
| Volume | 276 |
| Issue number | 23 |
| DOIs | |
| State | Published - Jun 8 2001 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
}
Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax. / Cuddeback, Sandy M.; Yamaguchi, Hirohito; Komatsu, Kiyoshi; Miyashita, Toshiyuki; Yamada, Masao; Wu, Chun; Singh, Sujay; Wang, Hong-Gang.
In: Journal of Biological Chemistry, Vol. 276, No. 23, 08.06.2001, p. 20559-20565.Research output: Contribution to journal › Article
TY - JOUR
T1 - Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax
AU - Cuddeback, Sandy M.
AU - Yamaguchi, Hirohito
AU - Komatsu, Kiyoshi
AU - Miyashita, Toshiyuki
AU - Yamada, Masao
AU - Wu, Chun
AU - Singh, Sujay
AU - Wang, Hong-Gang
PY - 2001/6/8
Y1 - 2001/6/8
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0035827622&partnerID=8YFLogxK
U2 - 10.1074/jbc.M101527200
DO - 10.1074/jbc.M101527200
M3 - Article
C2 - 11259440
AN - SCOPUS:0035827622
VL - 276
SP - 20559
EP - 20565
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 23
ER -