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Cytochrome c Release and Apoptosis Induced by Mitochondrial Targeting of Nuclear Orphan Receptor TR3
Hui Li,1Siva Kumar Kolluri,1Jian Gu,1Marcia I. Dawson,2Xihua Cao,1Peter D. Hobbs,3Bingzhen Lin,1Guo-quen Chen,1Jiang-song Lu,4Feng Lin,1Zhihua Xie,1Joseph A. Fontana,4John C. Reed,1Xiao-kun Zhang1*
TR3, an immediate-early response gene and an orphan member of the
steroid-thyroid hormone-retinoid receptor superfamily oftranscription
factors, regulates apoptosis through an unknownmechanism. In response
to apoptotic stimuli, TR3 translocatesfrom the nucleus to mitochondria
to induce cytochrome c releaseand apoptosis. Mitochondrial targeting
of TR3, but not its DNAbinding and transactivation, is essential for
its proapoptoticeffect. Our results reveal a mechanism by which a
nuclear transcriptionfactor translocates to mitochondria to initiate
apoptosis.
1 The Burnham Institute, 10901 North Torrey
Pines Road, La Jolla, CA 92037, USA.
2 Molecular
Medicine Research Institute, 325 East Middlefield Road, Mountain View,
CA 94043, USA.
3 Retinoid Program, SRI, Menlo Park,
CA 94025, USA.
4 Karmanos Cancer Institute, Wayne
State University, and the John D. Dingel VA Medical Center, 4646 John R
Street, Detroit, MI 48201, USA.
*
To whom correspondence should be addressed: E-mail:
xzhang{at}burnham-inst.org
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PERSPECTIVES
Catherine Brenner and Guido Kroemer (18 August 2000) Science289 (5482), 1150.
[DOI: 10.1126/science.289.5482.1150] |Summary »|Full Text »
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Mitochondrial Dysfunction Is Involved in Apoptosis Induced by Serum Withdrawal and Fatty Acids in the {beta}-Cell Line Ins-1.
I. Maestre, J. Jordan, S. Calvo, J. A. Reig, V. Cena, B. Soria, M. Prentki, and E. Roche (2003)
Endocrinology
144, 335-345
|Abstract »|Full Text »|PDF »
Caspase- and Serine Protease-dependent Apoptosis by the Death Domain of FADD in Normal Epithelial Cells.
J. Thorburn, L. M. Bender, M. J. Morgan, and A. Thorburn (2003)
Mol. Biol. Cell
14, 67-77
|Abstract »|Full Text »
The Embryonic Function of Germ Cell Nuclear Factor Is Dependent on the DNA Binding Domain.
Z.-J. Lan, A. C.-K. Chung, X. Xu, F. J. DeMayo, and A. J. Cooney (2002)
J. Biol. Chem.
277, 50660-50667
|Abstract »|Full Text »|PDF »
Elucidation of Molecular Events Mediating Induction of Apoptosis by Synthetic Retinoids Using a CD437-resistant Ovarian Carcinoma Cell Line.
W. F. Holmes, D. R. Soprano, and K. J. Soprano (2002)
J. Biol. Chem.
277, 45408-45419
|Abstract »|Full Text »|PDF »
Bcl-XL Protects BimEL-induced Bax Conformational Change and Cytochrome c Release Independent of Interacting with Bax or BimEL.
Dual roles of Nur77 in selective regulation of apoptosis and cell cycle by TPA and ATRA in gastric cancer cells.
Q. Wu, S. Liu, X.-f. Ye, Z.-w. Huang, and W.-j. Su (2002)
Carcinogenesis
23, 1583-1592
|Abstract »|Full Text »|PDF »
NF-{kappa}B Regulation in Human Neutrophils by Nuclear I{kappa}B{alpha}: Correlation to Apoptosis.
S. Castro-Alcaraz, V. Miskolci, B. Kalasapudi, D. Davidson, and I. Vancurova (2002)
J. Immunol.
169, 3947-3953
|Abstract »|Full Text »|PDF »
Trafficking of Ganglioside GD3 to Mitochondria by Tumor Necrosis Factor-alpha.
C. Garcia-Ruiz, A. Colell, A. Morales, M. Calvo, C. Enrich, and J. C. Fernandez-Checa (2002)
J. Biol. Chem.
277, 36443-36448
|Abstract »|Full Text »|PDF »
