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Contents |
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439 a.a.
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63 a.a.
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297 a.a.
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* Residue conservation analysis
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PDB id:
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| Name: |
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Gene regulation/signalling protein/DNA
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Title:
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Crystal structure of the csl-notch-mastermind ternary complex bound to DNA
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Structure:
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5'-d( Tp Tp Ap Cp Tp Gp Tp Gp Gp Gp Ap Ap Ap Gp A)-3'. Chain: b. Engineered: yes. 5'-d( Ap Ap Tp Cp Tp Tp Tp Cp Cp Cp Ap Cp Ap Gp T)-3'. Chain: c. Engineered: yes. Lin-12 and glp-1 phenotype protein 1, isoform b. Chain: a. Fragment: core (residues 192-663).
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Source:
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Synthetic: yes. Other_details: the sequence comes from a region within the mammalian hes-1 promoter. Caenorhabditis elegans. Organism_taxid: 6239. Gene: lag-1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: sel-8, lag-3.
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Biol. unit:
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Pentamer (from
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Resolution:
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3.12Å
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R-factor:
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0.273
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R-free:
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0.340
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Authors:
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J.J.Wilson,R.A.Kovall
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Key ref:
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J.J.Wilson
and
R.A.Kovall
(2006).
Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA.
Cell,
124,
985-996.
PubMed id:
DOI:
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Date:
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12-Jan-06
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Release date:
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21-Mar-06
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PROCHECK
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Headers
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References
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V6CLJ5
(V6CLJ5_CAEEL) -
Suppressor of hairless protein homolog from Caenorhabditis elegans
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Seq:
Struc:
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790 a.a.
439 a.a.
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DOI no:
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Cell
124:985-996
(2006)
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PubMed id:
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Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA.
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J.J.Wilson,
R.A.Kovall.
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ABSTRACT
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Notch signaling mediates communication between cells and is essential for proper
embryonic patterning and development. CSL is a DNA binding transcription factor
that regulates transcription of Notch target genes by interacting with
coregulators. Transcriptional activation requires the displacement of
corepressors from CSL by the intracellular portion of the receptor Notch
(NotchIC) and the recruitment of the coactivator protein Mastermind to the
complex. Here we report the 3.1 A structure of the ternary complex formed by
CSL, NotchIC, and Mastermind bound to DNA. As expected, the RAM domain of Notch
interacts with the beta trefoil domain of CSL; however, the C-terminal domain of
CSL has an unanticipated central role in the interface formed with the Notch
ankyrin repeats and Mastermind. Ternary complex formation induces a substantial
conformational change within CSL, suggesting a molecular mechanism for the
conversion of CSL from a repressor to an activator.
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Selected figure(s)
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Figure 1.
Figure 1. The CSL-NotchIC-Mastermind Ternary Complex
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Figure 4.
Figure 4. Electrostatic Surface Analysis of Ternary Complex
Interfaces
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2006,
124,
985-996)
copyright 2006.
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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
|
|
Reference
|
|
|
|
|
|
D.J.O'Donovan,
I.Stokes-Rees,
Y.Nam,
S.C.Blacklow,
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A.T.Brunger,
and
P.Sliz
(2012).
A grid-enabled web service for low-resolution crystal structure refinement.
|
| |
Acta Crystallogr D Biol Crystallogr,
68,
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|
|
|
|
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|
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(2012).
Objective assessment of cancer genes for drug discovery.
|
| |
Nat Rev Drug Discov,
12,
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and
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(2011).
Elevated β-arrestin1 expression correlated with risk stratification in acute lymphoblastic leukemia.
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| |
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M.Janz,
B.Dörken,
and
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(2011).
High-level expression of Mastermind-like 2 contributes to aberrant activation of the NOTCH signaling pathway in human lymphomas.
|
| |
Oncogene,
30,
1831-1840.
|
|
|
|
|
|
|
M.A.Calderwood,
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A.M.Holthaus,
S.C.Blacklow,
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(2011).
Epstein-Barr virus nuclear protein 3C binds to the N-terminal (NTD) and beta trefoil domains (BTD) of RBP/CSL; only the NTD interaction is essential for lymphoblastoid cell growth.
|
| |
Virology,
414,
19-25.
|
|
|
|
|
|
|
R.Schwanbeck,
S.Martini,
K.Bernoth,
and
U.Just
(2011).
The Notch signaling pathway: molecular basis of cell context dependency.
|
| |
Eur J Cell Biol,
90,
572-581.
|
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|
|
|
|
|
S.A.Wacker,
C.Alvarado,
G.von Wichert,
U.Knippschild,
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H.Hameister,
B.Baumann,
T.Borggrefe,
W.Knöchel,
and
F.Oswald
(2011).
RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.
|
| |
EMBO J,
30,
43-56.
|
|
|
|
|
|
|
Y.Wang,
Y.Liu,
S.N.Malek,
P.Zheng,
and
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(2011).
Targeting HIF1α eliminates cancer stem cells in hematological malignancies.
|
| |
Cell Stem Cell,
8,
399-411.
|
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|
|
|
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|
C.Del Bianco,
A.Vedenko,
S.H.Choi,
M.F.Berger,
L.Shokri,
M.L.Bulyk,
and
S.C.Blacklow
(2010).
Notch and MAML-1 complexation do not detectably alter the dna binding specificity of the transcription factor CSL.
|
| |
PLoS One,
5,
e15034.
|
|
|
|
|
|
|
D.R.Friedmann,
and
R.A.Kovall
(2010).
Thermodynamic and structural insights into CSL-DNA complexes.
|
| |
Protein Sci,
19,
34-46.
|
|
|
PDB code:
|
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|
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|
|
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J.S.Yuan,
P.C.Kousis,
S.Suliman,
I.Visan,
and
C.J.Guidos
(2010).
Functions of notch signaling in the immune system: consensus and controversies.
|
| |
Annu Rev Immunol,
28,
343-365.
|
|
|
|
|
|
|
K.L.Arnett,
M.Hass,
D.G.McArthur,
M.X.Ilagan,
J.C.Aster,
R.Kopan,
and
S.C.Blacklow
(2010).
Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes.
|
| |
Nat Struct Mol Biol,
17,
1312-1317.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
S.E.Johnson,
M.X.Ilagan,
R.Kopan,
and
D.Barrick
(2010).
Thermodynamic analysis of the CSL x Notch interaction: distribution of binding energy of the Notch RAM region to the CSL beta-trefoil domain and the mode of competition with the viral transactivator EBNA2.
|
| |
J Biol Chem,
285,
6681-6692.
|
|
|
|
|
|
|
D.Barrick
(2009).
Biological regulation via ankyrin repeat folding.
|
| |
ACS Chem Biol,
4,
19-22.
|
|
|
|
|
|
|
E.Gazave,
P.Lapébie,
G.S.Richards,
F.Brunet,
A.V.Ereskovsky,
B.M.Degnan,
C.Borchiellini,
M.Vervoort,
and
E.Renard
(2009).
Origin and evolution of the Notch signalling pathway: an overview from eukaryotic genomes.
|
| |
BMC Evol Biol,
9,
249.
|
|
|
|
|
|
|
G.P.Dotto
(2009).
Crosstalk of Notch with p53 and p63 in cancer growth control.
|
| |
Nat Rev Cancer,
9,
587-595.
|
|
|
|
|
|
|
M.L.Hansson,
A.E.Popko-Scibor,
M.Saint Just Ribeiro,
B.M.Dancy,
M.J.Lindberg,
P.A.Cole,
and
A.E.Wallberg
(2009).
The transcriptional coactivator MAML1 regulates p300 autoacetylation and HAT activity.
|
| |
Nucleic Acids Res,
37,
2996-3006.
|
|
|
|
|
|
|
R.E.Moellering,
M.Cornejo,
T.N.Davis,
C.Del Bianco,
J.C.Aster,
S.C.Blacklow,
A.L.Kung,
D.G.Gilliland,
G.L.Verdine,
and
J.E.Bradner
(2009).
Direct inhibition of the NOTCH transcription factor complex.
|
| |
Nature,
462,
182-188.
|
|
|
|
|
|
|
R.Kopan,
and
M.X.Ilagan
(2009).
The canonical Notch signaling pathway: unfolding the activation mechanism.
|
| |
Cell,
137,
216-233.
|
|
|
|
|
|
|
W.R.Gordon,
M.Roy,
D.Vardar-Ulu,
M.Garfinkel,
M.R.Mansour,
J.C.Aster,
and
S.C.Blacklow
(2009).
Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL.
|
| |
Blood,
113,
4381-4390.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
Y.Izumiya,
C.Izumiya,
D.Hsia,
T.J.Ellison,
P.A.Luciw,
and
H.J.Kung
(2009).
NF-kappaB serves as a cellular sensor of Kaposi's sarcoma-associated herpesvirus latency and negatively regulates K-Rta by antagonizing the RBP-Jkappa coactivator.
|
| |
J Virol,
83,
4435-4446.
|
|
|
|
|
|
|
A.S.McElhinny,
J.L.Li,
and
L.Wu
(2008).
Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways.
|
| |
Oncogene,
27,
5138-5147.
|
|
|
|
|
|
|
A.Smerdel-Ramoya,
S.Zanotti,
V.Deregowski,
and
E.Canalis
(2008).
Connective tissue growth factor enhances osteoblastogenesis in vitro.
|
| |
J Biol Chem,
283,
22690-22699.
|
|
|
|
|
|
|
C.Del Bianco,
J.C.Aster,
and
S.C.Blacklow
(2008).
Mutational and energetic studies of Notch 1 transcription complexes.
|
| |
J Mol Biol,
376,
131-140.
|
|
|
|
|
|
|
C.T.Ong,
J.R.Sedy,
K.M.Murphy,
and
R.Kopan
(2008).
Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition.
|
| |
PLoS ONE,
3,
e2823.
|
|
|
|
|
|
|
D.Barrick,
D.U.Ferreiro,
and
E.A.Komives
(2008).
Folding landscapes of ankyrin repeat proteins: experiments meet theory.
|
| |
Curr Opin Struct Biol,
18,
27-34.
|
|
|
|
|
|
|
D.Bellavia,
S.Checquolo,
A.F.Campese,
M.P.Felli,
A.Gulino,
and
I.Screpanti
(2008).
Notch3: from subtle structural differences to functional diversity.
|
| |
Oncogene,
27,
5092-5098.
|
|
|
|
|
|
|
D.Maier,
A.X.Chen,
A.Preiss,
and
M.Ketelhut
(2008).
The tiny Hairless protein from Apis mellifera: a potent antagonist of Notch signaling in Drosophila melanogaster.
|
| |
BMC Evol Biol,
8,
175.
|
|
|
|
|
|
|
D.R.Friedmann,
J.J.Wilson,
and
R.A.Kovall
(2008).
RAM-induced allostery facilitates assembly of a notch pathway active transcription complex.
|
| |
J Biol Chem,
283,
14781-14791.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
E.Kloss,
N.Courtemanche,
and
D.Barrick
(2008).
Repeat-protein folding: new insights into origins of cooperativity, stability, and topology.
|
| |
Arch Biochem Biophys,
469,
83-99.
|
|
|
|
|
|
|
J.C.Aster,
W.S.Pear,
and
S.C.Blacklow
(2008).
Notch signaling in leukemia.
|
| |
Annu Rev Pathol,
3,
587-613.
|
|
|
|
|
|
|
L.Poellinger,
and
U.Lendahl
(2008).
Modulating Notch signaling by pathway-intrinsic and pathway-extrinsic mechanisms.
|
| |
Curr Opin Genet Dev,
18,
449-454.
|
|
|
|
|
|
|
M.Fukami,
Y.Wada,
M.Okada,
F.Kato,
N.Katsumata,
T.Baba,
K.Morohashi,
J.Laporte,
M.Kitagawa,
and
T.Ogata
(2008).
Mastermind-like domain-containing 1 (MAMLD1 or CXorf6) transactivates the Hes3 promoter, augments testosterone production, and contains the SF1 target sequence.
|
| |
J Biol Chem,
283,
5525-5532.
|
|
|
|
|
|
|
M.Le Gall,
C.De Mattei,
and
E.Giniger
(2008).
Molecular separation of two signaling pathways for the receptor, Notch.
|
| |
Dev Biol,
313,
556-567.
|
|
|
|
|
|
|
R.A.Kovall
(2008).
More complicated than it looks: assembly of Notch pathway transcription complexes.
|
| |
Oncogene,
27,
5099-5109.
|
|
|
|
|
|
|
T.Shimizu,
T.Kagawa,
T.Inoue,
A.Nonaka,
S.Takada,
H.Aburatani,
and
T.Taga
(2008).
Stabilized beta-catenin functions through TCF/LEF proteins and the Notch/RBP-Jkappa complex to promote proliferation and suppress differentiation of neural precursor cells.
|
| |
Mol Cell Biol,
28,
7427-7441.
|
|
|
|
|
|
|
W.R.Gordon,
K.L.Arnett,
and
S.C.Blacklow
(2008).
The molecular logic of Notch signaling--a structural and biochemical perspective.
|
| |
J Cell Sci,
121,
3109-3119.
|
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|
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|
A.C.Nagel,
I.Wech,
D.Schwinkendorf,
and
A.Preiss
(2007).
Involvement of co-repressors Groucho and CtBP in the regulation of single-minded in Drosophila.
|
| |
Hereditas,
144,
195-205.
|
|
|
|
|
|
|
A.Krejcí,
and
S.Bray
(2007).
Notch activation stimulates transient and selective binding of Su(H)/CSL to target enhancers.
|
| |
Genes Dev,
21,
1322-1327.
|
|
|
|
|
|
|
C.Y.Peng,
H.Yajima,
C.E.Burns,
L.I.Zon,
S.S.Sisodia,
S.L.Pfaff,
and
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(2007).
Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord.
|
| |
Neuron,
53,
813-827.
|
|
|
|
|
|
|
D.F.Kelly,
R.J.Lake,
T.Walz,
and
S.Artavanis-Tsakonas
(2007).
Conformational variability of the intracellular domain of Drosophila Notch and its interaction with Suppressor of Hairless.
|
| |
Proc Natl Acad Sci U S A,
104,
9591-9596.
|
|
|
|
|
|
|
J.K.Takeuchi,
H.Lickert,
B.W.Bisgrove,
X.Sun,
M.Yamamoto,
K.Chawengsaksophak,
H.Hamada,
H.J.Yost,
J.Rossant,
and
B.G.Bruneau
(2007).
Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry.
|
| |
Proc Natl Acad Sci U S A,
104,
846-851.
|
|
|
|
|
|
|
K.Lefort,
A.Mandinova,
P.Ostano,
V.Kolev,
V.Calpini,
I.Kolfschoten,
V.Devgan,
J.Lieb,
W.Raffoul,
D.Hohl,
V.Neel,
J.Garlick,
G.Chiorino,
and
G.P.Dotto
(2007).
Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases.
|
| |
Genes Dev,
21,
562-577.
|
|
|
|
|
|
|
M.L.Coleman,
M.A.McDonough,
K.S.Hewitson,
C.Coles,
J.Mecinovic,
M.Edelmann,
K.M.Cook,
M.E.Cockman,
D.E.Lancaster,
B.M.Kessler,
N.J.Oldham,
P.J.Ratcliffe,
and
C.J.Schofield
(2007).
Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor.
|
| |
J Biol Chem,
282,
24027-24038.
|
|
|
PDB codes:
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|
|
|
|
|
|
|
O.Y.Lubman,
M.X.Ilagan,
R.Kopan,
and
D.Barrick
(2007).
Quantitative dissection of the Notch:CSL interaction: insights into the Notch-mediated transcriptional switch.
|
| |
J Mol Biol,
365,
577-589.
|
|
|
|
|
|
|
R.A.Kovall
(2007).
Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex.
|
| |
Curr Opin Struct Biol,
17,
117-127.
|
|
|
|
|
|
|
S.J.Kugler,
and
A.C.Nagel
(2007).
putzig is required for cell proliferation and regulates notch activity in Drosophila.
|
| |
Mol Biol Cell,
18,
3733-3740.
|
|
|
|
|
|
|
S.Rydziel,
L.Stadmeyer,
S.Zanotti,
D.Durant,
A.Smerdel-Ramoya,
and
E.Canalis
(2007).
Nephroblastoma overexpressed (Nov) inhibits osteoblastogenesis and causes osteopenia.
|
| |
J Biol Chem,
282,
19762-19772.
|
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|
|
|
|
|
T.Oyama,
K.Harigaya,
A.Muradil,
K.Hozumi,
S.Habu,
H.Oguro,
A.Iwama,
K.Matsuno,
R.Sakamoto,
M.Sato,
N.Yoshida,
and
M.Kitagawa
(2007).
Mastermind-1 is required for Notch signal-dependent steps in lymphocyte development in vivo.
|
| |
Proc Natl Acad Sci U S A,
104,
9764-9769.
|
|
|
|
|
|
|
T.Vilimas,
J.Mascarenhas,
T.Palomero,
M.Mandal,
S.Buonamici,
F.Meng,
B.Thompson,
C.Spaulding,
S.Macaroun,
M.L.Alegre,
B.L.Kee,
A.Ferrando,
L.Miele,
and
I.Aifantis
(2007).
Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia.
|
| |
Nat Med,
13,
70-77.
|
|
|
|
|
|
|
X.Zhu,
J.Wang,
B.G.Ju,
and
M.G.Rosenfeld
(2007).
Signaling and epigenetic regulation of pituitary development.
|
| |
Curr Opin Cell Biol,
19,
605-611.
|
|
|
|
|
|
|
Y.Nam,
P.Sliz,
W.S.Pear,
J.C.Aster,
and
S.C.Blacklow
(2007).
Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcription.
|
| |
Proc Natl Acad Sci U S A,
104,
2103-2108.
|
|
|
|
|
|
|
Y.Zhao,
R.B.Katzman,
L.M.Delmolino,
I.Bhat,
Y.Zhang,
C.B.Gurumurthy,
A.Germaniuk-Kurowska,
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H.Band,
and
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The notch regulator MAML1 interacts with p53 and functions as a coactivator.
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J Biol Chem,
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M.Fujimuro
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Uirusu,
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S.J.Bray
(2006).
Notch signalling: a simple pathway becomes complex.
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Nat Rev Mol Cell Biol,
7,
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Role of the RAM domain and ankyrin repeats on notch signaling and activity in cells of osteoblastic lineage.
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J Bone Miner Res,
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|
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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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