Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death

• Published in: Oncogene Vol. 18; no. 46; pp. 6183 - 6190
• Main Authors: LEE, J.-H, TAKAHASHI, T, YASUHARA, N, INAZAWA, J, KAMADA, S, TSUJIMOTO, Y
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 04.11.1999; Nature Publishing Group
• Subjects: Adaptor Proteins, Signal Transducing; Ageing, cell death; Amino Acid Sequence; Animals; Apoptosis; Apoptosis - physiology; Apoptosis Regulatory Proteins; B-Lymphocytes - chemistry; BAX protein; Bcl-2 protein; Binding Sites; Biological and medical sciences; Bis protein; Carrier Proteins - genetics; Carrier Proteins - isolation & purification; Carrier Proteins - metabolism; Cell death; Cell physiology; Chromosome 10; Chromosome Mapping; Chromosomes, Human, Pair 10 - genetics; Cloning, Molecular; DNA, Complementary - genetics; Fas antigen; Fundamental and applied biological sciences. Psychology; Genes; Homology; Humans; Immunoprecipitation; Mice; Molecular and cellular biology; Molecular Sequence Data; Organ Specificity; Protein Structure, Tertiary; Proteins; Proto-Oncogene Proteins c-bcl-2 - physiology; Sequence Alignment; Sequence Homology, Amino Acid; Transfection; Genetic mapping; Human; Binding protein; Nucleotide sequence; Molecular interaction; Chromosome C10; Gene expression; Synergism; Apoptosis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203043

Bcl-2 is the best characterized inhibitor of apoptosis, although the molecular basis of this action is not fully understood. Using a protein interaction cloning procedure, we identified a human gene designated as bis (mapped to chromosome 10q25) that encoded a novel Bcl-2-interacting protein. Bis protein showed no significant homology with Bcl-2 family proteins and had no prominent functional motif. Co-immunoprecipitation analysis confirmed that Bis interacted with Bcl-2 in vivo. DNA transfection experiments indicated that Bis itself exerted only weak anti-apoptotic activity, but was synergistic with Bcl-2 in preventing Bax-induced and Fas-mediated apoptosis. These results suggest that Bis is a novel modulator of cellular anti-apoptotic activity that functions through its interaction with Bcl-2.