Publication Date:
2001-04-28
Description:
Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049805/" 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/PMC3049805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wei, M C -- Zong, W X -- Cheng, E H -- Lindsten, T -- Panoutsakopoulou, V -- Ross, A J -- Roth, K A -- MacGregor, G R -- Thompson, C B -- Korsmeyer, S J -- 5T32AT09361/AT/NCCIH NIH HHS/ -- R01 HD036437-02/HD/NICHD NIH HHS/ -- R01 HD036437-03/HD/NICHD NIH HHS/ -- R01 HD036437-04/HD/NICHD NIH HHS/ -- R01 HD036437-05/HD/NICHD NIH HHS/ -- R01CA50239/CA/NCI NIH HHS/ -- R37CA4802/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Apr 27;292(5517):727-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Departments of Pathology and Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11326099" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies
;
Antigens, CD95/immunology/physiology
;
Apoptosis/*physiology
;
BH3 Interacting Domain Death Agonist Protein
;
Biopolymers
;
Carrier Proteins/genetics/metabolism
;
Cells, Cultured
;
Cytochrome c Group/metabolism
;
Endoplasmic Reticulum/metabolism
;
Etoposide/pharmacology
;
Hepatocytes/cytology/metabolism
;
Intracellular Membranes/metabolism
;
Membrane Proteins/genetics/*metabolism
;
Mice
;
Mitochondria/*metabolism
;
Protein Structure, Tertiary
;
Proto-Oncogene Proteins/genetics/*metabolism
;
*Proto-Oncogene Proteins c-bcl-2
;
Signal Transduction
;
Staurosporine/pharmacology
;
Transfection
;
Ultraviolet Rays
;
bcl-2 Homologous Antagonist-Killer Protein
;
bcl-2-Associated X Protein
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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