XX
XX
XX
FA MyoD
XX
SY MEF1; Myf-3 (human);
MyoD; MyoD1.
XX
OS mouse, Mus musculus
OC eukaryota;
animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia;
OC eutheria; rodentia; myomorpha; muridae; murinae
XX
XX
CL C0010; bHLH; 1.2.2.0.1.
XX
SZ 318 AA; 34.2 kDa
(cDNA), 45 kDa (SDS)
XX
XX
SC SwissProt #P10085
XX
FT 1 53 transcription activation domain.
FT 1 109 PF01586;
Basic.
FT 1 114 SM00520; BASIC.
FT 10 47 acidic region
(13/38).
FT 57 167 contains recognition site for Hsp90.
FT 100 112 nuclear localization signal (NLS234) [1].
FT 102
121 basic region.
FT 110 161 PF00010; HLH.
FT 115 166
SM00353; HLH.
FT 122 162 helix-loop-helix domain.
FT 122
136 helix 1.
FT 130 135 nuclear localization signal (NLS6)
[1].
FT 137 145 loop.
FT 146 162 helix 2.
FT 189 262
serine-/threonine-rich region (20/74).
FT 263 311 proline-rich
region (12/49).
XX
SF spectroscopic data: CD [15] [14],
EPR [15];
SF crystal structure [5];
SF heterodimers with
E12/E47 bind more avidly to DNA than homodimers [37] [25]
SF [26];
SF the heterodimer is identical to the DNA-binding
activity MEF-1 [26];
SF A114 is essential for DNA-binding,
T115 for muscle-specific transcriptional
SF activation [29];
SF both residues are buried at the protein-DNA interface and may
determine the
SF conformation at R111 which makes a base-specific
contact in the major
SF groove [5] [13] [6];
SF L122 discirminates
agianst c-Myc binding sites [21];
SF the DNA-binding specificity
differs slightly between MyoD homodimers and
SF MyoD/E12 or
MyoD/E47 heterodimers [33];
SF the HLH dimerization domain
forms a parallel four-helix-bundle [15];
SF DNA-binding induces
the basic region to adopt alpha-helical conformation
SF [15];
SF correct folding may be augmented by hsp90 which, however, is
not part of
SF the DNA-bound complex [8] [16] [7];
SF
KD (homodimer) = 31.2 uM, KD (MyoD/E47) = 0.72 uM, KD (MyoD/Id)
= 0.7 uM
SF [14];
SF MyoD/Id complexes form heterotetramers
with KD (tetramer/dimer) = 0.01 uM
SF [14];
SF the trans-activating
domain is masked [29];
SF both nuclear localization signal
function independently of each other [1];
XX
CP proliferating
myoblasts and differentiated myotubes
XX
FF transcriptional
activator [36] of muscle-specific genes [43];
FF myogenic
master gene product causing myogenic differentiation [48] [47]
FF [41];
FF inhibitor of cell proliferation depending on the
HLH domain [34] [35];
FF can partly substitute for Myf-5 and
vice versa [23];
FF induced immediately after mesoderm induction
between the first and second
FF phase of MRF4 expression [41]
[12];
FF in regenerating skeletal muscle for at least 2 weeks
[17];
FF positive autoregulation [44];
FF positively regulated
by thyroid hormone, antagonized by an overlapping AP-1
FF
element [20] [2];
FF for onset of MyoD expression, a dephosphorylation
step is required [22];
FF negative regulation of MyoD by ras,
c-fos, c-jun, junB, c-myc [46] [42]
FF [18] [19];
FF the
N-terminal part of c-Jun directly interacts with the HLH domain
of MyoD
FF [19] [24];
FF direct interaction with the pocket
domain of Rb protein is required for
FF myogenesis, maintenance
of the differentiated state, and repression of cell
FF proliferation
[10];
FF hyperphosphorylation upon association with E47 [26];
XX
IN T00131; c-Jun; mouse, Mus musculus.
IN T00204; E12;
human, Homo sapiens.
IN T00675; E12; rat, Rattus norvegicus.
IN T01787; E12; clawed frog, Xenopus laevis.
IN T00207; E47;
human, Homo sapiens.
IN T00674; E47; rat, Rattus norvegicus.
IN T01788; E47; mouse, Mus musculus.
IN T01454; Hsp90; mouse,
Mus musculus.
IN T01606; Id1.25; rat, Rattus norvegicus.
IN T00403; Id1; mouse, Mus musculus.
IN T01807; Id1; rat,
Rattus norvegicus.
IN T00404; Id2; mouse, Mus musculus.
IN T01212; Id2; human, Homo sapiens.
IN T00405; IEBP1; rat,
Rattus norvegicus.
IN T00432; ITF-1; human, Homo sapiens.
IN T00433; ITF-2; human, Homo sapiens.
IN T01784; MEF-2 (516
AA); clawed frog, Xenopus laevis.
IN T00505; MEF-2; mouse,
Mus musculus.
IN T01005; MEF-2; human, Homo sapiens.
IN
T01769; MEF-2C; mouse, Mus musculus.
IN T02506; MEF-2D (506
AA form); mouse, Mus musculus.
IN T02505; MEF-2D (514 AA form);
mouse, Mus musculus.
IN T01771; MEF-2D; clawed frog, Xenopus
laevis.
IN T01770; MEF-2DAB; human, Homo sapiens.
IN T00526;
MyoD; mouse, Mus musculus.
IN T01427; p300; human, Homo sapiens.
IN T00722; pRb; human, Homo sapiens.
IN T01423; pRb; mouse,
Mus musculus.
IN T01790; SCBPalpha; rat, Rattus norvegicus.
IN T01791; SCBPbeta; rat, Rattus norvegicus.
IN T01789; SCBPgamma;
rat, Rattus norvegicus.
XX
XX
XX
XX
RN [1];
RE0005811.
RX MEDLINE; 95273420.
RA Vandromme M., Cavadore
J.-C., Bonnieu A., Froeschle A., Lamb N., Fernandez
RA A.
RT Two nuclear localization signals present in the basic-helix
1 domains of
RT MyoD promote its active nuclear translocation
and can function independly
RL Proc. Natl. Acad. Sci. USA
92:4646-4650 (1995).
RN [2]; RE0003240.
RX MEDLINE; 94173724.
RA Muscat G. E. O., Mynett-Johnson L., Dowhan D., Downes M., Griggs
R.
RT Activation of MyoD gene transcription by 3, 4, 3'-triiodo-L-thyronine:
a
RT direct role for the thyroid hormone and retinoid X receptors
RL Nucleic Acids Res. 22:583-591 (1994).
RN [3]; RE0003241.
RX MEDLINE; 94165103.
RA Pedraza-Alva G., Zingg J. M., Jost
J. P.
RT AP-1 binds to a putative cAMP response element of
the MyoD1 promoter and
RT negatively modulates MyoD1 expression
in dividing myoblasts
RL J. Biol. Chem. 269:6978-6985 (1994).
RN [4]; RE0003242.
RX MEDLINE; 95047366.
RA Weintraub
H., Genetta T., Kadesch T.
RT Tissue-specific gene activation
by MyoD: determination of specificity by
RT cis-acting repression
elements
RL Genes Dev. 8:2203-2211 (1994).
RN [5]; RE0003392.
RX MEDLINE; 94236689.
RA Ma P. C. M., Rould M. A., Weintraub
H., Pabo C. O.
RT Crystal structure of MyoD bHLH domain-DNA
complex: perspectives on DNA
RT recognition and implications
for transcriptional activation
RL Cell 77:451-459 (1994).
RN [6]; RE0003394.
RX MEDLINE; 94139661.
RA Ferre-D'Amare
A. R., Pognonec P., Roeder R. G., Burley S. K.
RT Structure
and function of the b/HLH/Z domain of USF
RL EMBO J. 13:180-189
(1994).
RN [7]; RE0003416.
RX MEDLINE; 94132038.
RA
Shue G., Kohtz D.
RT Structural and functional aspects of
basic helix-loop-helix protein folding
RT by heat-shock protein
RL J. Biol. Chem. 269:2707-2711 (1994).
RN [8]; RE0003232.
RX MEDLINE; 93342016.
RA Thayer M. J., Weintraub H.
RT
A cellular factor stimulates the DNA-binding activity of MyoD
and E47
RL Proc. Natl. Acad. Sci. USA 90:6483-6487 (1993).
RN [9]; RE0003234.
RX MEDLINE; 93252867.
RA Winter B.,
Braun T., Arnold H. H.
RT cAMP-dependent protein kinase represses
myogenic differentiation and the
RT activity of the muscle-specific
helix-loop-helix transcription factors
RT Myf-5 and MyoD
RL J. Biol. Chem. 13:9869-9878 (1993).
RN [10]; RE0003236.
RX MEDLINE; 93161408.
RA Gu W., Schneider J. W., Condorelli
G., Kaushal S., Mahdavi V., Nadal-Ginard
RA B.
RT Interaction
of myogenic factors and the retinoblastoma protein mediates
RT muscle cell commitment and differentiation
RL Cell 72:309-324
(1993).
RN [11]; RE0003238.
RX MEDLINE; 93376736.
RA Hollenberg S. M., Cheng P. F., Weintraub H.
RT Use of a
conditional MyoD transcription factor in studies of MyoD
RT
trans-activation and muscle determination
RL Proc. Natl. Acad.
Sci. USA 90:8028-8032 (1993).
RN [12]; RE0003239.
RX MEDLINE;
94094328.
RA Rudnicki M. A., Schnegelsberg P. N. J., Stead
R. H., Braun T., Arnold H.
RA H., Jaenisch R.
RT MyoD
or Myf-5 is required for the formation of skeletal muscle
RL Cell 75:1351-1359 (1993).
RN [13]; RE0003393.
RX MEDLINE;
93241312.
RA Ferre-D'Amare A. E., Prendergast G. C., Ziff
E. B., Burley S. K.
RT Recognition by Max of its cognate DNA
through a dimeric b/HLH/Z domain
RL Nature 363:38-45 (1993).
RN [14]; RE0003415.
RX MEDLINE; 94068414.
RA Fairman R.,
Beran-Steed R. K., Anthony-Cahill S. J., Lear J. D., Stafford
RA III W. F., DeGrado W. F., Benfield P. A., Brenner S. L.
RT Multiple oligomeric states regulate the DNA binding of helix-loop-helix
RT proteins
RL Proc. Natl. Acad. Sci. USA 90:10429-10433 (1993).
RN [15]; RE0002662.
RX MEDLINE; 92188160.
RA Anthony-Cahill
S. J., Benfield P. A., Fairman R., Wasserman Z. R., Brenner
RA S. L., Stafford III W. F., Altenbach C., Hubbell W. L., DeGrado
W. F.
RT Molecular characterization of helix-loop-helix peptides
RL Science 255:979-983 (1992).
RN [16]; RE0002942.
RX
MEDLINE; 93024452.
RA Shaknovich R., Shue G., Kohtz D. S.
RT Conformational activation of a basic helix-loop-helix protein
(MyoD1) by
RT the C-terminal region of murine HSP90 (HSP84)
RL Mol. Cell. Biol. 12:5059-5068 (1992).
RN [17]; RE0003222.
RX MEDLINE; 92173253.
RA Fuechtbauer E. M., Westphal H.
RT MyoD and myogenin are coexpressed in regulating skeletal muscle
of the mouse
RL Dev. Dyn. 193:34-39 (1992).
RN [18]; RE0003223.
RX MEDLINE; 91203907.
RA Miner J. H., Wold B. J.
RT c-myc
inhibition of MyoD and myogenin-initiated myogenic differentiation
RL Mol. Cell. Biol. 11:2842-2851 (1992).
RN [19]; RE0003225.
RX MEDLINE; 92217746.
RA Li L., Chambard J. C., Karin M.,
Olson E. N.
RT Fos and Jun repress transcriptional activation
by myogenin and MyoD: the
RT amino terminus of Jun can mediate
repression
RL Genes Dev. 6:676-689 (1992).
RN [20]; RE0003226.
RX MEDLINE; 93024475.
RA Carnac G., Albagli-Curiel O., Vandromme
M., Pinset C., Montarras D., Laudet
RA V., Bonnieu A.
RT 3, 5, 3 - triiodothyronine positively regulates both MyoD1
gene
RT transcription and terminal differentiation in C2 myoblasts
RL Mol. Endocrinol. 6:1185-1194 (1992).
RN [21]; RE0003227.
RX MEDLINE; 93028394.
RA van Antwerp M. E., Chen D. G., Chang
C., Prochownik E. V.
RT A point mutation in MyoD basic domain
imparts c-Myc-like properties
RL Proc. Natl. Acad. Sci. USA
89:9010-9014 (1992).
RN [22]; RE0003228.
RX MEDLINE; 92340566.
RA Kim S. J., Kim K. Y., Tapscott S. J., Winokur T. S., Park K.,
Fujiki H.,
RA Weintraub H., Roberts A. B.
RT Inhibition
of protein phosphatases blocks myogenesis by first altering MyoD
RT binding activity
RL J. Biol. Chem. 267:15140-15145 (1992).
RN [23]; RE0003244.
RX MEDLINE; 93046639.
RA Rudnicki
M. A., Braun T., Hinuma S., Jaenisch R.
RT Inactivation of
MyoD in mice leads to up-regulation of the myogenic HLH
RT
gene Myf-5 and results in apparently normal muscle development
RL Cell 71:383-390 (1992).
RN [24]; RE0003418.
RX MEDLINE;
92154666.
RA Bengal E., Ransone L., Scharfmann R., Dwarki
V. J., Tapscott S. J.,
RA Weintraub H., Verma I. M.
RT
Functional antagonism between c-Jun and MyoD proteins: a direct
physical
RT association
RL Cell 68:507-519 (1992).
RN [25]; RE0000231.
RX MEDLINE; 91105861.
RA Sun X.-H.,
Baltimore D.
RT An inhibitory domain of E12 transcription
factor prevents DNA binding in
RT E12 homodimers but not in
E12 heterodimers
RL Cell 64:459-470 (1991).
RN [26]; RE0000238.
RX MEDLINE; 91309143.
RA Lassar A. B., Davis R. L., Wright
W. E., Kadesch T., Murre C., Voronova A.,
RA Baltimore D.,
Weintraub H.
RT Functional activity of myogenic HLH proteins
requires
RT hetero-oligomerization with E12/E47-like proteins
in vivo
RL Cell 66:305-315 (1991).
RN [27]; RE0000968.
RX MEDLINE; 91131581.
RA Chakraborty T., Brennan T., Olson
E.
RT Differential trans-activation of a muscle-specific enhancer
by myogenic
RT helix-loop-helix proteins is separable from
DNA binding
RL J. Biol. Chem. 266:2878-2882 (1991).
RN
[28]; RE0001620.
RX MEDLINE; 91203863.
RA French B. A.,
Chow K.-L., Olson E. N., Schwartz R. J.
RT Heterodimers of
myogenic helix-loop-helix regulatory factors and E12 bind a
RT complex element governing myogenic induction of the avian cardiac
RT alpha-actin promoter
RL Mol. Cell. Biol. 11:2439-2450 (1991).
RN [29]; RE0003414.
RX MEDLINE; 91331309.
RA Weintraub
H., Dwarki V. J., Verma I., Davis R. L., Hollenberg S., Snider
RA L., Lassar A. B., Tapscott S. J.
RT Muscle-specific transcriptional
activation by MyoD
RL Genes Dev. 5:1377-1386 (1991).
RN
[30]; RE0000054.
RX MEDLINE; 90182663.
RA Davis R. L.,
Cheng P.-F., Lassar A. B., Weintraub H.
RT The MyoD DNA binding
domain contains a recognition code for muscle-specific
RT
gene activation
RL Cell 60:733-746 (1990).
RN [31]; RE0001507.
RX MEDLINE; 90318358.
RA Yutzey K. E., Rhodes S. J., Konieczny
S. F.
RT Differential trans activation associated with the
muscle regulatory factors
RT MyoD1, myogenin, and MRF4
RL Mol. Cell. Biol. 10:3934-3944 (1990).
RN [32]; RE0002458.
RX MEDLINE; 90332633.
RA Weintraub H., Davis R., Lockshon
D., Lassar A.
RT MyoD binds cooperatively to two sites in
a target enhancer sequence:
RT Occupancy of two sites is required
for activation
RL Proc. Natl. Acad. Sci. USA 87:5623-5627
(1990).
RN [33]; RE0002661.
RX MEDLINE; 91068002.
RA Blackwell T. K., Weintraub H.
RT Differences and similarities
in DNA-binding preferences of MyoD and E2A
RT protein complexes
revealed by binding site selection
RL Science 250:1104-1110
(1990).
RN [34]; RE0003218.
RX MEDLINE; 90294926.
RA Sorrentino V., Pepperkok R., Davis R. L., Ansorge W., Philipson
L.
RT Cell proliferation inhibited by MyoD1 independently
of myogenic
RT differentiation
RL Nature 345:813-815 (1990).
RN [35]; RE0003417.
RX MEDLINE; 91046013.
RA Crescenzi
M., Fleming T. P., Lassar A. B., Weintraub H., Aaronson S. A.
RT MyoD induces growth arrest independent of differentiation in
normal and
RT transformed cells
RL Proc. Natl. Acad. Sci.
USA 87:8442-8446 (1990).
RN [36]; RE0000052.
RX MEDLINE;
89376533.
RA Lassar A. B., Buskin J. B., Lockshon D., Davis
R. L., Apone S., Hauschka S.
RA D., Weintraub H.
RT MyoD
is a sequence-specific DNA-binding protein requiring a region
of myc
RT homology to bind to the muscle creatine kinase enhancer
RL Cell 58:823-831 (1989).
RN [37]; RE0000053.
RX MEDLINE;
89336785.
RA Murre C., McCaw P. S., Vaessin H., Caudy M.,
Jan L. Y., Jan Y. N., Cabrera
RA C. V., Buskin J. N., Hauschka
S. D., Lassar A. B., Weintraub H., Baltimore
RA D.
RT
Interactions between heterologous helix-loop-helix proteins generate
RT complexes that bind specifically to a common DNA sequence
RL Cell 58:537-544 (1989).
RN [38]; RE0000092.
RX MEDLINE;
89168418.
RA Murre C., McCaw P. S., Baltimore D.
RT A
new DNA binding and dimerization motif in immunoglobulin enhancer
RT binding, daughterless, MyoD, and myc proteins
RL Cell 56:777-783
(1989).
RN [39]; RE0000703.
RX MEDLINE; 90185184.
RA Rhodes S. J., Konieczny S. F.
RT Identification of MRF4:
a new member of the muscle regulatory factor gene
RT family
RL Genes Dev. 3:2050-2061 (1989).
RN [40]; RE0001484.
RX MEDLINE; 90014819.
RA Vaidya T. B., Rhodes S. J., Taparowsky
E. J., Konieczny S. F.
RT Fibroblast growth factor and transforming
growth factor beta repress
RT transcription of the myogenic
regulatory gene MyoD1
RL Mol. Cell. Biol. 9:3576-3579 (1989).
RN [41]; RE0003213.
RX MEDLINE; 90015111.
RA Sassoon D.,
Lyons G., Wright W. E., Lin V., Lassar A. B., Weintraub H.,
RA Buckingham M.
RT Expression of two myogenic regulatory
factors myogenin and MyoD1 during
RT mouse embryogenesis
RL Nature 341:303-307 (1989).
RN [42]; RE0003214.
RX MEDLINE;
89354541.
RA Lassar A. B., Thayer M. J., Overell R. W., Weintraub
H.
RT Transformation by activated ras or fos prevents myogenesis
by inhibiting
RT expression of MyoD1
RL Cell 58:659-667
(1989).
RN [43]; RE0003215.
RX MEDLINE; 89315811.
RA Weintraub H., Tapscott S. J., Davis R. L., Thayer M. J., Adam
M. A., Lassar
RA A. B., Miller A. D.
RT Activation of
muscle-specific genes in pigment, nerve, fat, liver, and
RT
fibroblast cell lines by forced expression of MyoD
RL Proc.
Natl. Acad. Sci. USA 86:5434-5438 (1989).
RN [44]; RE0003216.
RX MEDLINE; 89324070.
RA Thayer M. J., Tapscott S. J., Davis
R. L., Wright W. E., Lassar A. B.,
RA Weintraub H.
RT
Positive autoregulation of the myogenic determination gene MyoD1
RL Cell 58:241-248 (1989).
RN [45]; RE0002654.
RX MEDLINE;
89019371.
RA Tapscott S. J., Davis R. L., Thayer M. J., Cheng
P., Weintraub H., Lassar
RA A. B.
RT MyoD1: a nuclear
phosphoprotein requiring a Myc homology region to convert
RT fibroblasts to myoblasts
RL Science 242:405-411 (1988).
RN [46]; RE0003172.
RX MEDLINE; 87257922.
RA Olson E.N.,
Spizz G., Tainsky M.A.
RT The Oncogenic Forms of N-ras or
H-ras Prevent Skeletal Myoblast
RT Differentiation
RL
Mol. Cell. Biol. 7:2104-2111 (1987).
RN [47]; RE0003212.
RX MEDLINE; 88080485.
RA Davis R. L., Weintraub H., Lassar
A. B.
RT Expression of a single transfected cDNA converts
fibroblasts into myoblasts
RL Cell 51:987-1000 (1987).
RN [48]; RE0003211.
RX MEDLINE; 87051736.
RA Lassar A.
B., Paterson B. M., Weintraub H.
RT Transfection of a DNA
locus that mediates the conversion of 10T1/2
RT fibroblasts
into myoblasts
RL Cell 47:649-656 (1986).
XX