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  • 1
    Publication Date: 2008-10-25
    Description: BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597110/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597110/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gavathiotis, Evripidis -- Suzuki, Motoshi -- Davis, Marguerite L -- Pitter, Kenneth -- Bird, Gregory H -- Katz, Samuel G -- Tu, Ho-Chou -- Kim, Hyungjin -- Cheng, Emily H-Y -- Tjandra, Nico -- Walensky, Loren D -- 5P01CA92625/CA/NCI NIH HHS/ -- 5R01CA125562/CA/NCI NIH HHS/ -- 5R01CA50239/CA/NCI NIH HHS/ -- K99 HL095929/HL/NHLBI NIH HHS/ -- K99 HL095929-01A1/HL/NHLBI NIH HHS/ -- K99 HL095929-02/HL/NHLBI NIH HHS/ -- R00 HL095929/HL/NHLBI NIH HHS/ -- R01 CA050239/CA/NCI NIH HHS/ -- R01 CA125562/CA/NCI NIH HHS/ -- R01 CA125562-02/CA/NCI NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1076-81. doi: 10.1038/nature07396.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948948" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis ; Apoptosis Regulatory Proteins/chemistry/metabolism ; BH3 Interacting Domain Death Agonist Protein/metabolism ; Cell Line ; *Gene Expression Regulation ; Humans ; Membrane Proteins/chemistry/metabolism ; Mice ; Mutagenesis, Site-Directed ; Mutation/genetics ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Proto-Oncogene Proteins/chemistry/metabolism ; Sequence Alignment ; bcl-2-Associated X Protein/chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Los Angeles, Alejandro -- Ferrari, Francesco -- Fujiwara, Yuko -- Mathieu, Ronald -- Lee, Soohyun -- Lee, Semin -- Tu, Ho-Chou -- Ross, Samantha -- Chou, Stephanie -- Nguyen, Minh -- Wu, Zhaoting -- Theunissen, Thorold W -- Powell, Benjamin E -- Imsoonthornruksa, Sumeth -- Chen, Jiekai -- Borkent, Marti -- Krupalnik, Vladislav -- Lujan, Ernesto -- Wernig, Marius -- Hanna, Jacob H -- Hochedlinger, Konrad -- Pei, Duanqing -- Jaenisch, Rudolf -- Deng, Hongkui -- Orkin, Stuart H -- Park, Peter J -- Daley, George Q -- Nature. 2015 Dec 16. doi: 10.1038/nature16479.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26675720" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-09-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Los Angeles, Alejandro -- Ferrari, Francesco -- Fujiwara, Yuko -- Mathieu, Ronald -- Lee, Soohyun -- Lee, Semin -- Tu, Ho-Chou -- Ross, Samantha -- Chou, Stephanie -- Nguyen, Minh -- Wu, Zhaoting -- Theunissen, Thorold W -- Powell, Benjamin E -- Imsoonthornruksa, Sumeth -- Chen, Jiekai -- Borkent, Marti -- Krupalnik, Vladislav -- Lujan, Ernesto -- Wernig, Marius -- Hanna, Jacob H -- Hochedlinger, Konrad -- Pei, Duanqing -- Jaenisch, Rudolf -- Deng, Hongkui -- Orkin, Stuart H -- Park, Peter J -- Daley, George Q -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Sep 24;525(7570):E6-9. doi: 10.1038/nature15513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Transplantation Program, Division of Pediatric Hematology Oncology, Children's Hospital Boston, and Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA. ; Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USApeter_park@hms.harvard.edu. ; Children's Hospital &Harvard Stem Cell Institute Flow Cytometry Research Facility, Children's Hospital Boston, Boston, Massachusetts 02115, USA. ; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. ; South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. ; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, Massachusetts 02114, USA. ; Department of Development and Reproduction, Erasmus Medical Center, 3015 CN Rotterdam, Netherlands. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA. ; College of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26399835" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2010-04-01
    Print ISSN: 0360-3199
    Electronic ISSN: 1879-3487
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by Elsevier
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