MyoD
Encyclopedia
MyoD is a protein
with a key role in regulating muscle
differentiation
. MyoD belongs to a family of proteins known as myogenic regulatory factors
(MRFs). These bHLH (basic helix loop helix) transcription factor
s act sequentially in myogenic differentiation. MRF family members include MyoD, Myf5
, myogenin
, and MRF4 (Myf6).
MyoD is one of the earliest markers of myogenic commitment. MyoD is expressed in activated satellite cells, but not in quiescent satellite cells. Although MyoD marks myoblast commitment, muscle development is not dramatically ablated in mouse mutants lacking the MyoD gene. This is likely to be due to functional redundancy from Myf5.
levels are also reported to be elevated in aging skeletal muscle.
One of the main actions of MyoD is to remove cells from the cell cycle
(halt proliferation) by enhancing the transcription of p21
. MyoD is inhibited by cyclin dependent kinases (CDK
s). CDKs are in turn inhibited by p21. Thus MyoD enhances its own activity in the cell.
with HDAC1
, ID1
, ID2
, Retinoblastoma protein
, STAT3
, CSRP3
, Cyclin-dependent kinase 4
, CREB-binding protein, TCF3
, MOS
, EP300
, C-jun
, Cyclin-dependent kinase inhibitor 1C
, Retinoid X receptor alpha
and MDFI
.
is a positive cofactor of MyoD, as it cooperates with MyoD at inducing the transcriptional activity of MEF2C
(by displacing HDAC4
from MEF2C); moreover IFRD1 also represses the transcriptional activity of NF-kB
, which is known to inhibit MyoD mRNA accumulation.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
with a key role in regulating muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
. MyoD belongs to a family of proteins known as myogenic regulatory factors
Myogenic regulatory factors
Myogenic regulatory factors are basic-helix-loop-helix transcription factors that regulate myogenesis: MyoD, Myf5, myogenin, and MRF4.These proteins contain a conserved basic DNA binding domain that binds the E box DNA motif . They dimerize with other HLH containing proteins through an HLH-HLH...
(MRFs). These bHLH (basic helix loop helix) transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s act sequentially in myogenic differentiation. MRF family members include MyoD, Myf5
Myf5
Myf5 is a protein with a key role in regulating muscle differentiation.Myf5 belongs to a family of proteins known as myogenic regulatory factors . These bHLH transcription factors act sequentially in myogenic differentiation. MRF family members include Myf5, MyoD , myogenin, and MRF4 ....
, myogenin
Myogenin
Myogenin , also known as MYOG, is a gene.Myogenin is a muscle-specific basic-helix-loop-helix transcription factor involved in the coordination of skeletal muscle development and repair...
, and MRF4 (Myf6).
MyoD is one of the earliest markers of myogenic commitment. MyoD is expressed in activated satellite cells, but not in quiescent satellite cells. Although MyoD marks myoblast commitment, muscle development is not dramatically ablated in mouse mutants lacking the MyoD gene. This is likely to be due to functional redundancy from Myf5.
Functions of MyoD
The function of MyoD in development is to commit mesoderm cells to a skeletal lineage, and then to regulate that process. MyoD may also play a role in regulating muscle repair. MyoD mRNAMessenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
levels are also reported to be elevated in aging skeletal muscle.
One of the main actions of MyoD is to remove cells from the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
(halt proliferation) by enhancing the transcription of p21
P21
p21 / WAF1 also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 is a protein that in humans is encoded by the CDKN1A gene located on chromosome 6 .- Function :...
. MyoD is inhibited by cyclin dependent kinases (CDK
Cyclin-dependent kinase
thumb|350px|Schematic of the cell cycle. outer ring: I=[[Interphase]], M=[[Mitosis]]; inner ring: M=Mitosis; G1=[[G1 phase|Gap phase 1]]; S=[[S phase|Synthesis]]; G2=[[G2 phase|Gap phase 2]]...
s). CDKs are in turn inhibited by p21. Thus MyoD enhances its own activity in the cell.
Interactions
MyoD has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with HDAC1
HDAC1
Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...
, ID1
ID1
DNA-binding protein inhibitor ID-1 is a protein that in mice and humans is encoded by the ID1 gene.. The protein encoded by this gene is a helix-loop-helix protein that can form heterodimers with members of the basic HLH family of transcription factors...
, ID2
ID2
DNA-binding protein inhibitor ID-2 is a protein that in humans is encoded by the ID2 gene.-Interactions:ID2 has been shown to interact with MyoD and NEDD9....
, Retinoblastoma protein
Retinoblastoma protein
The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in the majority types of cancer. One highly studied function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide...
, STAT3
STAT3
Signal transducer and activator of transcription 3 also known as STAT3 is a transcription factor which in humans is encoded by the STAT3 gene.- Function :The protein encoded by this gene is a member of the STAT protein family...
, CSRP3
CSRP3
Cysteine and glycine-rich protein 3 is a protein that in humans is encoded by the CSRP3 gene.- External links :*...
, Cyclin-dependent kinase 4
Cyclin-dependent kinase 4
Cyclin-dependent kinase 4 is part of the cyclin-dependent kinase family.It is regulated by Cyclin D.-Interactions:Cyclin-dependent kinase 4 has been shown to interact with SERTAD1, CDC37, CEBPA, PCNA, Cyclin D3, Cyclin D1, CDKN2C, MyoD, P16, CDKN2B, Drebrin-like and CDKN1B.-External links:...
, CREB-binding protein, TCF3
TCF3
Transcription factor 3 , also known as TCF3, is a protein that in humans is encoded by the TCF3 gene...
, MOS
MOS (gene)
Proto-oncogene serine/threonine-protein kinase mos is an enzyme that in humans is encoded by the MOS gene.-Interactions:MOS has been shown to interact with MyoD.-Further reading:...
, EP300
EP300
E1A binding protein p300 also known as EP300 or p300 is a protein that, in humans, is encoded by the EP300 gene. This protein regulates the activity of many genes in tissues throughout the body...
, C-jun
C-jun
c-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...
, Cyclin-dependent kinase inhibitor 1C
Cyclin-dependent kinase inhibitor 1C
Cyclin-dependent kinase inhibitor 1C , also known as CDKN1C, is protein which in humans is encoded by the CDKN1C imprinted gene.- Function :...
, Retinoid X receptor alpha
Retinoid X receptor alpha
Retinoid X receptor alpha , also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.- Function :...
and MDFI
MDFI
MyoD family inhibitor is a protein that in humans is encoded by the MDFI gene.-Interactions:MDFI has been shown to interact with C9orf86, MyoD, SIX1, Myogenin and GNAI2.-Further reading:...
.
Coactivators of MyoD
IFRD1IFRD1
Interferon-related developmental regulator 1 is a protein that in humans is encoded by the IFRD1 gene. The gene is expressed mostly in neutrophils, skeletal and cardiac muscle, brain, pancreas....
is a positive cofactor of MyoD, as it cooperates with MyoD at inducing the transcriptional activity of MEF2C
MEF2C
Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene. MEF2C is a transcription factor in the Mef2 family.-Genomics:...
(by displacing HDAC4
HDAC4
Histone deacetylase 4, also known as HDAC4, is a protein which in humans is encoded by the HDAC4 gene.- Function :Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects...
from MEF2C); moreover IFRD1 also represses the transcriptional activity of NF-kB
NF-kB
NF-κB is a protein complex that controls the transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens...
, which is known to inhibit MyoD mRNA accumulation.