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PDBsum entry 1gv4
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Oxidoreductase
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PDB id
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1gv4
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Contents |
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* Residue conservation analysis
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DOI no:
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Nat Struct Biol
9:442-446
(2002)
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PubMed id:
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The crystal structure of the mouse apoptosis-inducing factor AIF.
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M.J.Maté,
M.Ortiz-Lombardía,
B.Boitel,
A.Haouz,
D.Tello,
S.A.Susin,
J.Penninger,
G.Kroemer,
P.M.Alzari.
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ABSTRACT
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Mitochondria play a key role in apoptosis due to their capacity to release
potentially lethal proteins. One of these latent death factors is cytochrome c,
which can stimulate the proteolytic activation of caspase zymogens. Another
important protein is apoptosis-inducing factor (AIF), a flavoprotein that can
stimulate a caspase-independent cell-death pathway required for early embryonic
morphogenesis. Here, we report the crystal structure of mouse AIF at 2.0 A. Its
active site structure and redox properties suggest that AIF functions as an
electron transferase with a mechanism similar to that of the bacterial
ferredoxin reductases, its closest evolutionary homologs. However, AIF
structurally differs from these proteins in some essential features, including a
long insertion in a C-terminal beta-hairpin loop, which may be related to its
apoptogenic functions.
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Selected figure(s)
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Figure 1.
Figure 1. Overall structure of mouse AIF. a, Structural
comparison of AIF, GR and BphA4. FAD and NADH are shown in black
and cyan sticks, respectively. b, Crystallographic contacts in
AIF crystals. Monomers 2 and 3 form a crystallographic dimer
related by a two-fold axis. The Pro-rich C-terminal insertion is
stabilized by crystal contacts, as seen between monomers 1 and
2. c, Distribution of invariant residues (green) among mammalian
and D. discoideum AIFs in both faces of the monomer. The FAD
molecular surface is shown in magenta. The dimerization area is
marked and the two-fold axis is depicted by an arrow.
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Figure 3.
Figure 3. The crystallographic AIF dimer. The stereo view of
the surface of one crystallographic dimer is seen along the
z-axis, slightly away from the noncrystallographic two-fold
axis. The rendered surface is colored by electrostatic
potential. An arrowhead indicates the entrance of each
NADH-binding pocket.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2002,
9,
442-446)
copyright 2002.
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Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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L.Delavallée,
L.Cabon,
P.Galán-Malo,
H.K.Lorenzo,
and
S.A.Susin
(2011).
AIF-mediated caspase-independent necroptosis: A new chance for targeted therapeutics.
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IUBMB Life,
63,
221-232.
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C.Artus,
H.Boujrad,
A.Bouharrour,
M.N.Brunelle,
S.Hoos,
V.J.Yuste,
P.Lenormand,
J.C.Rousselle,
A.Namane,
P.England,
H.K.Lorenzo,
and
S.A.Susin
(2010).
AIF promotes chromatinolysis and caspase-independent programmed necrosis by interacting with histone H2AX.
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EMBO J,
29,
1585-1599.
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D.Ghezzi,
I.Sevrioukova,
F.Invernizzi,
C.Lamperti,
M.Mora,
P.D'Adamo,
F.Novara,
O.Zuffardi,
G.Uziel,
and
M.Zeviani
(2010).
Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor.
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Am J Hum Genet,
86,
639-649.
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E.Hangen,
D.De Zio,
M.Bordi,
C.Zhu,
P.Dessen,
F.Caffin,
S.Lachkar,
J.L.Perfettini,
V.Lazar,
J.Benard,
G.M.Fimia,
M.Piacentini,
F.Harper,
G.Pierron,
J.M.Vicencio,
P.Bénit,
A.de Andrade,
G.Höglinger,
C.Culmsee,
P.Rustin,
K.Blomgren,
F.Cecconi,
G.Kroemer,
and
N.Modjtahedi
(2010).
A brain-specific isoform of mitochondrial apoptosis-inducing factor: AIF2.
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Cell Death Differ,
17,
1155-1166.
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E.Hangen,
K.Blomgren,
P.Bénit,
G.Kroemer,
and
N.Modjtahedi
(2010).
Life with or without AIF.
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Trends Biochem Sci,
35,
278-287.
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K.Nishikawa,
Y.Shomura,
S.Kawasaki,
Y.Niimura,
and
Y.Higuchi
(2010).
Crystal structure of NADH:rubredoxin oxidoreductase from Clostridium acetobutylicum: a key component of the dioxygen scavenging system in obligatory anaerobes.
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Proteins,
78,
1066-1070.
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PDB code:
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L.J.Martin
(2010).
Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases.
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Pharmaceuticals (Basel),
3,
839-915.
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N.Joza,
J.A.Pospisilik,
E.Hangen,
T.Hanada,
N.Modjtahedi,
J.M.Penninger,
and
G.Kroemer
(2009).
AIF: not just an apoptosis-inducing factor.
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Ann N Y Acad Sci,
1171,
2.
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S.J.Chinta,
A.Rane,
N.Yadava,
J.K.Andersen,
D.G.Nicholls,
and
B.M.Polster
(2009).
Reactive oxygen species regulation by AIF- and complex I-depleted brain mitochondria.
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Free Radic Biol Med,
46,
939-947.
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T.Senda,
M.Senda,
S.Kimura,
and
T.Ishida
(2009).
Redox control of protein conformation in flavoproteins.
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Antioxid Redox Signal,
11,
1741-1766.
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Y.Wang,
V.L.Dawson,
and
T.M.Dawson
(2009).
Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos.
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Exp Neurol,
218,
193-202.
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I.Y.Churbanova,
and
I.F.Sevrioukova
(2008).
Redox-dependent changes in molecular properties of mitochondrial apoptosis-inducing factor.
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J Biol Chem,
283,
5622-5631.
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L.L.Chan,
M.Pineda,
J.T.Heeres,
P.J.Hergenrother,
and
B.T.Cunningham
(2008).
A general method for discovering inhibitors of protein-DNA interactions using photonic crystal biosensors.
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ACS Chem Biol,
3,
437-448.
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N.Joza,
K.Galindo,
J.A.Pospisilik,
P.Benit,
M.Rangachari,
E.E.Kanitz,
Y.Nakashima,
G.G.Neely,
P.Rustin,
J.M.Abrams,
G.Kroemer,
and
J.M.Penninger
(2008).
The molecular archaeology of a mitochondrial death effector: AIF in Drosophila.
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Cell Death Differ,
15,
1009-1018.
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G.Hagelueken,
L.Wiehlmann,
T.M.Adams,
H.Kolmar,
D.W.Heinz,
B.Tümmler,
and
W.D.Schubert
(2007).
Crystal structure of the electron transfer complex rubredoxin rubredoxin reductase of Pseudomonas aeruginosa.
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Proc Natl Acad Sci U S A,
104,
12276-12281.
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PDB codes:
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H.Jiang,
A.E.Talaska,
J.Schacht,
and
S.H.Sha
(2007).
Oxidative imbalance in the aging inner ear.
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Neurobiol Aging,
28,
1605-1612.
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H.K.Lorenzo,
and
S.A.Susin
(2007).
Therapeutic potential of AIF-mediated caspase-independent programmed cell death.
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Drug Resist Updat,
10,
235-255.
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M.Gong,
S.Hay,
K.R.Marshall,
A.W.Munro,
and
N.S.Scrutton
(2007).
DNA binding suppresses human AIF-M2 activity and provides a connection between redox chemistry, reactive oxygen species, and apoptosis.
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J Biol Chem,
282,
30331-30340.
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S.Krantic,
N.Mechawar,
S.Reix,
and
R.Quirion
(2007).
Apoptosis-inducing factor: a matter of neuron life and death.
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Prog Neurobiol,
81,
179-196.
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S.L.Mehta,
N.Manhas,
and
R.Raghubir
(2007).
Molecular targets in cerebral ischemia for developing novel therapeutics.
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Brain Res Rev,
54,
34-66.
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T.S.Collingwood,
E.V.Smirnova,
M.Bogush,
N.Carpino,
R.S.Annan,
and
A.Y.Tsygankov
(2007).
T-cell ubiquitin ligand affects cell death through a functional interaction with apoptosis-inducing factor, a key factor of caspase-independent apoptosis.
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J Biol Chem,
282,
30920-30928.
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A.G.Porter,
and
A.G.Urbano
(2006).
Does apoptosis-inducing factor (AIF) have both life and death functions in cells?
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Bioessays,
28,
834-843.
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C.Delettre,
V.J.Yuste,
R.S.Moubarak,
M.Bras,
J.C.Lesbordes-Brion,
S.Petres,
J.Bellalou,
and
S.A.Susin
(2006).
AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer.
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J Biol Chem,
281,
6413-6427.
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C.J.Yu,
L.T.Jia,
Y.L.Meng,
J.Zhao,
Y.Zhang,
X.C.Qiu,
Y.M.Xu,
W.H.Wen,
L.B.Yao,
D.M.Fan,
B.Q.Jin,
S.Y.Chen,
and
A.G.Yang
(2006).
Selective proapoptotic activity of a secreted recombinant antibody/AIF fusion protein in carcinomas overexpressing HER2.
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Gene Ther,
13,
313-320.
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J.M.Levitt,
A.Baldwin,
A.Papadakis,
S.Puri,
J.Xylas,
K.Münger,
and
I.Georgakoudi
(2006).
Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells.
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J Biomed Opt,
11,
064012.
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J.S.Armstrong
(2006).
Mitochondria: a target for cancer therapy.
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Br J Pharmacol,
147,
239-248.
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J.S.Armstrong
(2006).
Mitochondrial membrane permeabilization: the sine qua non for cell death.
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Bioessays,
28,
253-260.
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L.De Colibus,
and
A.Mattevi
(2006).
New frontiers in structural flavoenzymology.
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Curr Opin Struct Biol,
16,
722-728.
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L.Galluzzi,
N.Larochette,
N.Zamzami,
and
G.Kroemer
(2006).
Mitochondria as therapeutic targets for cancer chemotherapy.
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Oncogene,
25,
4812-4830.
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L.J.Martin
(2006).
Mitochondriopathy in Parkinson disease and amyotrophic lateral sclerosis.
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J Neuropathol Exp Neurol,
65,
1103-1110.
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L.J.Siskind,
R.N.Kolesnick,
and
M.Colombini
(2006).
Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations.
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Mitochondrion,
6,
118-125.
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N.Apostolova,
A.M.Cervera,
V.M.Victor,
S.Cadenas,
A.Sanjuan-Pla,
A.Alvarez-Barrientos,
J.V.Esplugues,
and
K.J.McCreath
(2006).
Loss of apoptosis-inducing factor leads to an increase in reactive oxygen species, and an impairment of respiration that can be reversed by antioxidants.
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Cell Death Differ,
13,
354-357.
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N.Hail,
B.Z.Carter,
M.Konopleva,
and
M.Andreeff
(2006).
Apoptosis effector mechanisms: a requiem performed in different keys.
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Apoptosis,
11,
889-904.
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N.Vahsen,
C.Candé,
P.Dupaigne,
F.Giordanetto,
R.T.Kroemer,
E.Herker,
S.Scholz,
N.Modjtahedi,
F.Madeo,
E.Le Cam,
and
G.Kroemer
(2006).
Physical interaction of apoptosis-inducing factor with DNA and RNA.
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Oncogene,
25,
1763-1774.
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V.P.van Empel,
A.T.Bertrand,
R.J.van Oort,
R.van der Nagel,
M.Engelen,
H.V.van Rijen,
P.A.Doevendans,
H.J.Crijns,
S.L.Ackerman,
W.Sluiter,
and
L.J.De Windt
(2006).
EUK-8, a superoxide dismutase and catalase mimetic, reduces cardiac oxidative stress and ameliorates pressure overload-induced heart failure in the harlequin mouse mutant.
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J Am Coll Cardiol,
48,
824-832.
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A.Urbano,
U.Lakshmanan,
P.H.Choo,
J.C.Kwan,
P.Y.Ng,
K.Guo,
S.Dhakshinamoorthy,
and
A.Porter
(2005).
AIF suppresses chemical stress-induced apoptosis and maintains the transformed state of tumor cells.
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EMBO J,
24,
2815-2826.
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B.M.Polster,
G.Basañez,
A.Etxebarria,
J.M.Hardwick,
and
D.G.Nicholls
(2005).
Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria.
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J Biol Chem,
280,
6447-6454.
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K.Samejima,
and
W.C.Earnshaw
(2005).
Trashing the genome: the role of nucleases during apoptosis.
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Nat Rev Mol Cell Biol,
6,
677-688.
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L.J.Siskind
(2005).
Mitochondrial ceramide and the induction of apoptosis.
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J Bioenerg Biomembr,
37,
143-153.
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L.J.Siskind,
S.Fluss,
M.Bui,
and
M.Colombini
(2005).
Sphingosine forms channels in membranes that differ greatly from those formed by ceramide.
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J Bioenerg Biomembr,
37,
227-236.
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M.Bras,
B.Queenan,
and
S.A.Susin
(2005).
Programmed cell death via mitochondria: different modes of dying.
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Biochemistry (Mosc),
70,
231-239.
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S.Sano,
S.Tao,
Y.Endo,
T.Inaba,
M.A.Hossain,
C.Miyake,
M.Matsuo,
H.Aoki,
K.Asada,
and
K.Saito
(2005).
Purification and cDNA cloning of chloroplastic monodehydroascorbate reductase from spinach.
|
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Biosci Biotechnol Biochem,
69,
762-772.
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B.Langley,
and
R.R.Ratan
(2004).
Oxidative stress-induced death in the nervous system: cell cycle dependent or independent?
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J Neurosci Res,
77,
621-629.
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C.Garrido,
and
G.Kroemer
(2004).
Life's smile, death's grin: vital functions of apoptosis-executing proteins.
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Curr Opin Cell Biol,
16,
639-646.
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C.M.Shih,
W.C.Ko,
J.S.Wu,
Y.H.Wei,
L.F.Wang,
E.E.Chang,
T.Y.Lo,
H.H.Cheng,
and
C.T.Chen
(2004).
Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts.
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J Cell Biochem,
91,
384-397.
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L.Du,
H.Bayir,
Y.Lai,
X.Zhang,
P.M.Kochanek,
S.C.Watkins,
S.H.Graham,
and
R.S.Clark
(2004).
Innate gender-based proclivity in response to cytotoxicity and programmed cell death pathway.
|
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J Biol Chem,
279,
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S.J.Hong,
T.M.Dawson,
and
V.L.Dawson
(2004).
Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling.
|
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Trends Pharmacol Sci,
25,
259-264.
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T.Liu,
B.Brouha,
and
D.Grossman
(2004).
Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells.
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Oncogene,
23,
39-48.
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C.M.Shih,
J.S.Wu,
W.C.Ko,
L.F.Wang,
Y.H.Wei,
H.F.Liang,
Y.C.Chen,
and
C.T.Chen
(2003).
Mitochondria-mediated caspase-independent apoptosis induced by cadmium in normal human lung cells.
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J Cell Biochem,
89,
335-347.
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J.A.Klein,
and
S.L.Ackerman
(2003).
Oxidative stress, cell cycle, and neurodegeneration.
|
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J Clin Invest,
111,
785-793.
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M.H.Hefti,
J.Vervoort,
and
W.J.van Berkel
(2003).
Deflavination and reconstitution of flavoproteins.
|
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Eur J Biochem,
270,
4227-4242.
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H.Ye,
C.Cande,
N.C.Stephanou,
S.Jiang,
S.Gurbuxani,
N.Larochette,
E.Daugas,
C.Garrido,
G.Kroemer,
and
H.Wu
(2002).
DNA binding is required for the apoptogenic action of apoptosis inducing factor.
|
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Nat Struct Biol,
9,
680-684.
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PDB code:
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S.A.Lipton,
and
E.Bossy-Wetzel
(2002).
Dueling activities of AIF in cell death versus survival: DNA binding and redox activity.
|
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Cell,
111,
147-150.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
