دورية أكاديمية
Bax homodimerization is not required for Bax to accelerate chemotherapy-induced cell death.
| العنوان: | Bax homodimerization is not required for Bax to accelerate chemotherapy-induced cell death. |
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| المؤلفون: | Simonian PL; Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. Gabriel.Nunez@umich.edu, Grillot DA, Andrews DW, Leber B, Nuñez G |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 1996 Dec 13; Vol. 271 (50), pp. 32073-7. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Apoptosis* , Proto-Oncogene Proteins c-bcl-2*, Proto-Oncogene Proteins/*metabolism, Animals ; Cell Line ; Cell Survival ; Cisplatin/pharmacology ; Electrophoresis, Polyacrylamide Gel ; Etoposide/pharmacology ; Fluorouracil/pharmacology ; Mutagenesis, Site-Directed ; Protein Conformation ; Proto-Oncogene Proteins/chemistry ; bcl-2-Associated X Protein |
| مستخلص: | Bax, a member of the Bcl-2 family of proteins, has been shown to accelerate apoptosis induced by growth factor withdrawal, gamma-irradiation, and the chemotherapeutic agent, etoposide. The mechanism by which Bax promotes apoptosis is poorly understood. Bax forms homodimers which have been suggested to act as accelerators or inducers of cell death. However, the requirement for homodimerization of Bax to promote cell death remains unclear. We performed site-directed mutagenesis of the BH1, BH2, and BH3 in Bax to determine the regions of Bax required for homodimerization and to define the role of Bax homodimers in cell death induced by chemotherapy drugs. Bax proteins expressing alanine substitutions of the highly conserved amino acids glycine 108 (G108) in BH1, tryptophan 158 (W158) in BH2, and glycine 67 and aspartic acid 68 (GD67-68) in BH3 as well as deletion of the most conserved amino acids in BH1 (Delta102-112) and BH2 (Delta151-159) and deletion of BH3 (Delta63-71) maintained their ability to accelerate chemotherapy-induced cell death. Immunoprecipitation studies revealed that Bax with deletions in BH1 and BH2 still associated with wild-type Bax while deletion of BH3 disrupted Bax homodimerization. These results demonstrate that Bax does not require the conserved regions of homology, BH1, BH2, or BH3, to accelerate chemotherapy-induced cell death. Furthermore, our results established BH3 as a region required for Bax homodimerization in mammalian cells and demonstrate that monomeric forms of Bax are active in accelerating cell death induced by chemotherapy agents. |
| معلومات مُعتمدة: | CA-64421 United States CA NCI NIH HHS; CA-64556 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Proto-Oncogene Proteins) 0 (Proto-Oncogene Proteins c-bcl-2) 0 (bcl-2-Associated X Protein) 6PLQ3CP4P3 (Etoposide) Q20Q21Q62J (Cisplatin) U3P01618RT (Fluorouracil) |
| تواريخ الأحداث: | Date Created: 19961213 Date Completed: 19970117 Latest Revision: 20210209 |
| رمز التحديث: | 20240627 |
| DOI: | 10.1074/jbc.271.50.32073 |
| PMID: | 8943258 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0021-9258 |
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| DOI: | 10.1074/jbc.271.50.32073 |