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Transcription/DNA
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PDB id
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1if1
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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Biological process
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regulation of transcription, DNA-dependent
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1 term
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Biochemical function
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regulatory region DNA binding
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2 terms
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DOI no:
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Nature
391:103-106
(1998)
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PubMed id:
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Structure of IRF-1 with bound DNA reveals determinants of interferon regulation.
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C.R.Escalante,
J.Yie,
D.Thanos,
A.K.Aggarwal.
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ABSTRACT
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The family of interferon regulatory factor (IRF) transcription factors is
important in the regulation of interferons in response to infection by virus and
in the regulation of interferon-inducible genes. The IRF family is characterized
by a unique 'tryptophan cluster' DNA-binding region. Here we report the crystal
structure of the IRF-1 region bound to the natural positive regulatory domain I
(PRD I) DNA element from the interferon-beta promoter. The structure provides
the first three-dimensional view of a member of the growing IRF family,
revealing a new helix-turn-helix motif that latches onto DNA through three of
the five conserved tryptophans. The motif selects a short GAAA core sequence
through an obliquely angled recognition helix, with an accompanying bending of
the DNA axis in the direction of the protein. Together, these features suggest a
basis for the occurrence of GAAA repeats within IRF response elements and
provide clues to the assembly of the higher-order interferon-beta enhancesome.
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Selected figure(s)
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Figure 3.
Figure 3 Protein-DNA interactions. a, A view along the IRF-1
recognition helix showing residues Arg 82, Cys 83, Asn 85 and
Ser 86 interacting with bases in the major groove. The figure
also shows two of the conserved tryptophans (Trp 38 and Trp 58)
straddling the major groove and contacting the DNA backbone. The
tryptophans are fixed in position through hydrophobic contacts
with residues within the interior of the protein, including two
phenylalanines (Phe 55 and Phe 81). Hydrogen bonds are shown in
yellow as dotted lines. The van der Waals contacts between Ser
86 and a thymine base are indicated by a white dashed line. b, A
sketch summarizing contacts between IRF-1 and DNA. The GAAA core
sequence, contacted in the major groove, is shaded. Contacts to
the DNA backbone arise from several segments of IRF-1, including
the three loops and the three  -helices.
Hydrogen bonds to bases and the backbone are shown as dotted and
dashed lines, respectively.
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Figure 4.
Figure 4 A model showing the van der Waals surfaces of the
DNA-binding regions of IRF-1 and the NF-  B
p50 homodimer bound to the PRD I and. PRD II elements of the
IFN-  promoter,
respectively. The NF- B
coordinates were extracted from the structure of NF- B
p50 homodimer bound to a B
site (GGGAATTCCC)22. The model reveals steric clashes between
the N-terminal arm of IRF-1 and the dimerization domain of NF-
B,
in accordance with the interference observed in vitro3. The DNA
probably bends further than shown in order to relieve clashes
between the specificity domain of NF- B
and the DNA backbone of the PRD I element.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(1998,
391,
103-106)
copyright 1998.
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Figures were
selected
by an automated process.
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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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|
A.Masumi
(2011).
Histone acetyltransferases as regulators of nonhistone proteins: the role of interferon regulatory factor acetylation on gene transcription.
|
| |
J Biomed Biotechnol, 2011,
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J.F.Liu,
X.D.Ding,
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Molecular characterization and association analysis of porcine interferon regulatory factor 1 gene.
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| |
Mol Biol Rep, 38,
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An extended set of PRDM1/BLIMP1 target genes links binding motif type to dynamic repression.
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| |
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Q.Y.Zhang,
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Identification and characterization of interferon regulatory factor-1 from orange-spotted grouper (Epinephelus coioides).
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| |
Mol Biol Rep, 37,
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H.J.Little,
N.K.Rorick,
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Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6.
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| |
Hum Mol Genet, 18,
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L.Yang,
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Q.Sun,
J.Hiscott,
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(2009).
Functional analysis of a dominant negative mutation of interferon regulatory factor 5.
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| |
PLoS ONE, 4,
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P.Génin,
A.Vaccaro,
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The role of differential expression of human interferon--a genes in antiviral immunity.
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| |
Cytokine Growth Factor Rev, 20,
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R.Janowski,
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S.H.Kaufmann,
and
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(2009).
Structural analysis reveals DNA binding properties of Rv2827c, a hypothetical protein from Mycobacterium tuberculosis.
|
| |
J Struct Funct Genomics, 10,
137-150.
|
|
|
PDB code:
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|
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V.Narayan,
M.Eckert,
A.Zylicz,
M.Zylicz,
and
K.L.Ball
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Cooperative regulation of the interferon regulatory factor-1 tumor suppressor protein by core components of the molecular chaperone machinery.
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| |
J Biol Chem, 284,
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|
|
|
|
|
|
|
A.Takaoka,
T.Tamura,
and
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Interferon regulatory factor family of transcription factors and regulation of oncogenesis.
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| |
Cancer Sci, 99,
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|
|
|
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|
P.Peixoto,
Y.Liu,
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M.P.Hildebrand,
D.W.Boykin,
C.Bailly,
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and
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Direct inhibition of the DNA-binding activity of POU transcription factors Pit-1 and Brn-3 by selective binding of a phenyl-furan-benzimidazole dication.
|
| |
Nucleic Acids Res, 36,
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|
|
|
|
|
|
|
T.Beck,
A.Krasauskas,
T.Gruene,
and
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(2008).
A magic triangle for experimental phasing of macromolecules.
|
| |
Acta Crystallogr D Biol Crystallogr, 64,
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|
|
|
PDB codes:
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|
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|
|
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|
|
T.Tamura,
H.Yanai,
D.Savitsky,
and
T.Taniguchi
(2008).
The IRF family transcription factors in immunity and oncogenesis.
|
| |
Annu Rev Immunol, 26,
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|
|
|
|
|
|
|
V.V.Hargreaves,
and
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The salt dependence of the interferon regulatory factor 1 DNA binding domain binding to DNA reveals ions are localized around protein and DNA.
|
| |
Biochemistry, 47,
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|
|
|
|
|
|
|
W.Chen,
S.S.Lam,
H.Srinath,
Z.Jiang,
J.J.Correia,
C.A.Schiffer,
K.A.Fitzgerald,
K.Lin,
and
W.E.Royer
(2008).
Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5.
|
| |
Nat Struct Mol Biol, 15,
1213-1220.
|
|
|
PDB code:
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|
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A.I.Dragan,
V.V.Hargreaves,
E.N.Makeyeva,
and
P.L.Privalov
(2007).
Mechanisms of activation of interferon regulator factor 3: the role of C-terminal domain phosphorylation in IRF-3 dimerization and DNA binding.
|
| |
Nucleic Acids Res, 35,
3525-3534.
|
|
|
|
|
|
|
A.Paun,
and
P.M.Pitha
(2007).
The IRF family, revisited.
|
| |
Biochimie, 89,
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|
|
|
|
|
|
|
C.R.Escalante,
E.Nistal-Villán,
L.Shen,
A.García-Sastre,
and
A.K.Aggarwal
(2007).
Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer.
|
| |
Mol Cell, 26,
703-716.
|
|
|
PDB code:
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|
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D.Panne,
T.Maniatis,
and
S.C.Harrison
(2007).
An atomic model of the interferon-beta enhanceosome.
|
| |
Cell, 129,
1111-1123.
|
|
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PDB codes:
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F.Schmitz,
A.Heit,
S.Guggemoos,
A.Krug,
J.Mages,
M.Schiemann,
H.Adler,
I.Drexler,
T.Haas,
R.Lang,
and
H.Wagner
(2007).
Interferon-regulatory-factor 1 controls Toll-like receptor 9-mediated IFN-beta production in myeloid dendritic cells.
|
| |
Eur J Immunol, 37,
315-327.
|
|
|
|
|
|
|
K.Ozato,
P.Tailor,
and
T.Kubota
(2007).
The interferon regulatory factor family in host defense: mechanism of action.
|
| |
J Biol Chem, 282,
20065-20069.
|
|
|
|
|
|
|
R.Joshi,
J.M.Passner,
R.Rohs,
R.Jain,
A.Sosinsky,
M.A.Crickmore,
V.Jacob,
A.K.Aggarwal,
B.Honig,
and
R.S.Mann
(2007).
Functional specificity of a Hox protein mediated by the recognition of minor groove structure.
|
| |
Cell, 131,
530-543.
|
|
|
PDB codes:
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B.Sun,
M.Chang,
D.Chen,
and
P.Nie
(2006).
Gene structure and transcription of IRF-2 in the mandarin fish Siniperca chuatsi with the finding of alternative transcripts and microsatellite in the coding region.
|
| |
Immunogenetics, 58,
774-784.
|
|
|
|
|
|
|
J.Y.Cheong,
S.W.Cho,
S.G.Chung,
J.A.Lee,
M.Yeo,
H.J.Wang,
J.E.Lee,
K.B.Hahm,
and
J.H.Kim
(2006).
Genetic polymorphism of interferon-gamma, interferon-gamma receptor, and interferon regulatory factor-1 genes in patients with hepatitis B virus infection.
|
| |
Biochem Genet, 44,
246-255.
|
|
|
|
|
|
|
K.Honda,
A.Takaoka,
and
T.Taniguchi
(2006).
Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors.
|
| |
Immunity, 25,
349-360.
|
|
|
|
|
|
|
M.Eckert,
S.E.Meek,
and
K.L.Ball
(2006).
A novel repressor domain is required for maximal growth inhibition by the IRF-1 tumor suppressor.
|
| |
J Biol Chem, 281,
23092-23102.
|
|
|
|
|
|
|
P.Prabakaran,
J.G.Siebers,
S.Ahmad,
M.M.Gromiha,
M.G.Singarayan,
and
A.Sarai
(2006).
Classification of protein-DNA complexes based on structural descriptors.
|
| |
Structure, 14,
1355-1367.
|
|
|
|
|
|
|
R.J.Richardson,
J.Dixon,
S.Malhotra,
M.J.Hardman,
L.Knowles,
R.P.Boot-Handford,
P.Shore,
A.Whitmarsh,
and
M.J.Dixon
(2006).
Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch.
|
| |
Nat Genet, 38,
1329-1334.
|
|
|
|
|
|
|
V.Bergan,
S.Steinsvik,
H.Xu,
Ã.˜.Kileng,
and
B.Robertsen
(2006).
Promoters of type I interferon genes from Atlantic salmon contain two main regulatory regions.
|
| |
FEBS J, 273,
3893-3906.
|
|
|
|
|
|
|
C.M.Robinson,
P.T.Hale,
and
J.M.Carlin
(2005).
The role of IFN-gamma and TNF-alpha-responsive regulatory elements in the synergistic induction of indoleamine dioxygenase.
|
| |
J Interferon Cytokine Res, 25,
20-30.
|
|
|
|
|
|
|
J.Zhang,
J.Wang,
C.Wood,
D.Xu,
and
L.Zhang
(2005).
Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 replication and transcription activator regulates viral and cellular genes via interferon-stimulated response elements.
|
| |
J Virol, 79,
5640-5652.
|
|
|
|
|
|
|
M.Upreti,
and
P.C.Rath
(2005).
Expression and DNA binding activity of the recombinant interferon regulatory factor-1 (IRF-1) of mouse.
|
| |
Mol Biol Rep, 32,
103-116.
|
|
|
|
|
|
|
B.J.Barnes,
J.Richards,
M.Mancl,
S.Hanash,
L.Beretta,
and
P.M.Pitha
(2004).
Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection.
|
| |
J Biol Chem, 279,
45194-45207.
|
|
|
|
|
|
|
B.Lubyova,
M.J.Kellum,
A.J.Frisancho,
and
P.M.Pitha
(2004).
Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7.
|
| |
J Biol Chem, 279,
7643-7654.
|
|
|
|
|
|
|
D.Panne,
T.Maniatis,
and
S.C.Harrison
(2004).
Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer.
|
| |
EMBO J, 23,
4384-4393.
|
|
|
PDB code:
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|
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|
|
N.Clarke,
A.M.Jimenez-Lara,
E.Voltz,
and
H.Gronemeyer
(2004).
Tumor suppressor IRF-1 mediates retinoid and interferon anticancer signaling to death ligand TRAIL.
|
| |
EMBO J, 23,
3051-3060.
|
|
|
|
|
|
|
A.Masumi,
Y.Yamakawa,
H.Fukazawa,
K.Ozato,
and
K.Komuro
(2003).
Interferon regulatory factor-2 regulates cell growth through its acetylation.
|
| |
J Biol Chem, 278,
25401-25407.
|
|
|
|
|
|
|
A.Moustakas,
and
C.H.Heldin
(2003).
The nuts and bolts of IRF structure.
|
| |
Nat Struct Biol, 10,
874-876.
|
|
|
|
|
|
|
B.J.Barnes,
A.E.Field,
and
P.M.Pitha-Rowe
(2003).
Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFNA enhanceosome in vivo and transcriptional activity of IFNA genes.
|
| |
J Biol Chem, 278,
16630-16641.
|
|
|
|
|
|
|
B.Y.Qin,
C.Liu,
S.S.Lam,
H.Srinath,
R.Delston,
J.J.Correia,
R.Derynck,
and
K.Lin
(2003).
Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation.
|
| |
Nat Struct Biol, 10,
913-921.
|
|
|
PDB code:
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|
|
|
|
|
|
|
C.M.Robinson,
K.A.Shirey,
and
J.M.Carlin
(2003).
Synergistic transcriptional activation of indoleamine dioxygenase by IFN-gamma and tumor necrosis factor-alpha.
|
| |
J Interferon Cytokine Res, 23,
413-421.
|
|
|
|
|
|
|
K.S.Childs,
and
S.Goodbourn
(2003).
Identification of novel co-repressor molecules for Interferon Regulatory Factor-2.
|
| |
Nucleic Acids Res, 31,
3016-3026.
|
|
|
|
|
|
|
R.L.Xie,
S.Gupta,
A.Miele,
D.Shiffman,
J.L.Stein,
G.S.Stein,
and
A.J.van Wijnen
(2003).
The tumor suppressor interferon regulatory factor 1 interferes with SP1 activation to repress the human CDK2 promoter.
|
| |
J Biol Chem, 278,
26589-26596.
|
|
|
|
|
|
|
A.Caillaud,
A.Prakash,
E.Smith,
A.Masumi,
A.G.Hovanessian,
D.E.Levy,
and
I.Marié
(2002).
Acetylation of interferon regulatory factor-7 by p300/CREB-binding protein (CBP)-associated factor (PCAF) impairs its DNA binding.
|
| |
J Biol Chem, 277,
49417-49421.
|
|
|
|
|
|
|
A.Kröger,
M.Köster,
K.Schroeder,
H.Hauser,
and
P.P.Mueller
(2002).
Activities of IRF-1.
|
| |
J Interferon Cytokine Res, 22,
5.
|
|
|
|
|
|
|
B.Barnes,
B.Lubyova,
and
P.M.Pitha
(2002).
On the role of IRF in host defense.
|
| |
J Interferon Cytokine Res, 22,
59-71.
|
|
|
|
|
|
|
C.M.Hu,
S.Y.Jang,
J.C.Fanzo,
and
A.B.Pernis
(2002).
Modulation of T cell cytokine production by interferon regulatory factor-4.
|
| |
J Biol Chem, 277,
49238-49246.
|
|
|
|
|
|
|
C.R.Escalante,
A.L.Brass,
J.M.Pongubala,
E.Shatova,
L.Shen,
H.Singh,
and
A.K.Aggarwal
(2002).
Crystal structure of PU.1/IRF-4/DNA ternary complex.
|
| |
Mol Cell, 10,
1097-1105.
|
|
|
|
|
|
|
C.R.Escalante,
L.Shen,
D.Thanos,
and
A.K.Aggarwal
(2002).
Structure of NF-kappaB p50/p65 heterodimer bound to the PRDII DNA element from the interferon-beta promoter.
|
| |
Structure, 10,
383-391.
|
|
|
PDB code:
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|
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|
|
|
E.Hinoi,
V.J.Balcar,
N.Kuramoto,
N.Nakamichi,
and
Y.Yoneda
(2002).
Nuclear transcription factors in the hippocampus.
|
| |
Prog Neurobiol, 68,
145-165.
|
|
|
|
|
|
|
J.Nehyba,
R.Hrdlicková,
J.Burnside,
and
H.R.Bose
(2002).
A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein.
|
| |
Mol Cell Biol, 22,
3942-3957.
|
|
|
|
|
|
|
L.H.Wong,
H.Sim,
M.Chatterjee-Kishore,
I.Hatzinisiriou,
R.J.Devenish,
G.Stark,
and
S.J.Ralph
(2002).
Isolation and characterization of a human STAT1 gene regulatory element. Inducibility by interferon (IFN) types I and II and role of IFN regulatory factor-1.
|
| |
J Biol Chem, 277,
19408-19417.
|
|
|
|
|
|
|
L.Zhang,
and
J.S.Pagano
(2002).
Structure and function of IRF-7.
|
| |
J Interferon Cytokine Res, 22,
95.
|
|
|
|
|
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PDB code:
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PDB codes:
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