MyoD

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Myogenic differentiation 1
Protein MYOD1 PDB 1mdy.png
PDB rendering based on 1mdy.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols MYOD1 ; MYF3; MYOD; PUM; bHLHc1
External IDs OMIM159970 MGI97275 HomoloGene7857 GeneCards: MYOD1 Gene
RNA expression pattern
PBB GE MYOD1 206657 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4654 17927
Ensembl ENSG00000129152 ENSMUSG00000009471
UniProt P15172 P10085
RefSeq (mRNA) NM_002478 NM_010866
RefSeq (protein) NP_002469 NP_034996
Location (UCSC) Chr 11:
17.74 – 17.74 Mb
Chr 7:
46.38 – 46.38 Mb
PubMed search [1] [2]

MyoD is a protein with a key role in regulating muscle differentiation. MyoD, which was discovered in the laboratory of Harold M. Weintraub, belongs to a family of proteins known as myogenic regulatory factors (MRFs).[1] These bHLH (basic helix loop helix) transcription factors 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. Nevertheless, the combination of MyoD and Myf5 is vital to the success of myogenesis.

Function[edit]

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 mRNA 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 (CDKs). CDKs are in turn inhibited by p21. Thus MyoD enhances its own activity in the cell.

Interactions[edit]

MyoD has been shown to interact with:

Coactivators[edit]

IFRD1 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-κB, which is known to inhibit MyoD mRNA accumulation.[24][25]

References[edit]

  1. ^ "Entrez Gene: MYOD1 myogenic differentiation 1". 
  2. ^ Bengal E, Ransone L, Scharfmann R, Dwarki VJ, Tapscott SJ, Weintraub H et al. (February 1992). "Functional antagonism between c-Jun and MyoD proteins: a direct physical association". Cell 68 (3): 507–19. PMID 1310896. 
  3. ^ Polesskaya A, Naguibneva I, Duquet A, Bengal E, Robin P, Harel-Bellan A (August 2001). "Interaction between acetylated MyoD and the bromodomain of CBP and/or p300". Mol. Cell. Biol. 21 (16): 5312–20. doi:10.1128/MCB.21.16.5312-5320.2001. PMC 87255. PMID 11463815. 
  4. ^ a b Sartorelli V, Huang J, Hamamori Y, Kedes L (February 1997). "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C". Mol. Cell. Biol. 17 (2): 1010–26. PMC 231826. PMID 9001254. 
  5. ^ Kong Y, Flick MJ, Kudla AJ, Konieczny SF (August 1997). "Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD". Mol. Cell. Biol. 17 (8): 4750–60. PMC 232327. PMID 9234731. 
  6. ^ Zhang JM, Zhao X, Wei Q, Paterson BM (December 1999). "Direct inhibition of G(1) cdk kinase activity by MyoD promotes myoblast cell cycle withdrawal and terminal differentiation". EMBO J. 18 (24): 6983–93. doi:10.1093/emboj/18.24.6983. PMC 1171761. PMID 10601020. 
  7. ^ Zhang JM, Wei Q, Zhao X, Paterson BM (February 1999). "Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4". EMBO J. 18 (4): 926–33. doi:10.1093/emboj/18.4.926. PMC 1171185. PMID 10022835. 
  8. ^ Reynaud EG, Leibovitch MP, Tintignac LA, Pelpel K, Guillier M, Leibovitch SA (June 2000). "Stabilization of MyoD by direct binding to p57(Kip2)". J. Biol. Chem. 275 (25): 18767–76. doi:10.1074/jbc.M907412199. PMID 10764802. 
  9. ^ Lau P, Bailey P, Dowhan DH, Muscat GE (January 1999). "Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD". Nucleic Acids Res. 27 (2): 411–20. PMC 148194. PMID 9862959. 
  10. ^ Puri PL, Iezzi S, Stiegler P, Chen TT, Schiltz RL, Muscat GE et al. (October 2001). "Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis". Mol. Cell 8 (4): 885–97. PMID 11684023. 
  11. ^ a b Mal A, Sturniolo M, Schiltz RL, Ghosh MK, Harter ML (April 2001). "A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program". EMBO J. 20 (7): 1739–53. doi:10.1093/emboj/20.7.1739. PMC 145490. PMID 11285237. 
  12. ^ Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E et al. (March 2004). "The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis". Nature 428 (6980): 328–32. doi:10.1038/nature02329. PMID 15029197. 
  13. ^ a b c Langlands K, Yin X, Anand G, Prochownik EV (August 1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". J. Biol. Chem. 272 (32): 19785–93. PMID 9242638. 
  14. ^ Finkel T, Duc J, Fearon ER, Dang CV, Tomaselli GF (January 1993). "Detection and modulation in vivo of helix-loop-helix protein-protein interactions". J. Biol. Chem. 268 (1): 5–8. PMID 8380166. 
  15. ^ Gupta K, Anand G, Yin X, Grove L, Prochownik EV (March 1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. PMID 9528857. 
  16. ^ McLoughlin P, Ehler E, Carlile G, Licht JD, Schäfer BW (October 2002). "The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein". J. Biol. Chem. 277 (40): 37045–53. doi:10.1074/jbc.M203336200. PMID 12145280. 
  17. ^ Ling MT, Chiu YT, Lee TK, Leung SC, Fung MK, Wang X et al. (September 2008). "Id-1 induces proteasome-dependent degradation of the HBX protein". J. Mol. Biol. 382 (1): 34–43. doi:10.1016/j.jmb.2007.06.020. PMID 18674781. 
  18. ^ Chen CM, Kraut N, Groudine M, Weintraub H (September 1996). "I-mf, a novel myogenic repressor, interacts with members of the MyoD family". Cell 86 (5): 731–41. PMID 8797820. 
  19. ^ Lenormand JL, Benayoun B, Guillier M, Vandromme M, Leibovitch MP, Leibovitch SA (February 1997). "Mos activates myogenic differentiation by promoting heterodimerization of MyoD and E12 proteins". Mol. Cell. Biol. 17 (2): 584–93. PMC 231783. PMID 9001211. 
  20. ^ Gu W, Schneider JW, Condorelli G, Kaushal S, Mahdavi V, Nadal-Ginard B (February 1993). "Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation". Cell 72 (3): 309–24. PMID 8381715. 
  21. ^ Froeschlé A, Alric S, Kitzmann M, Carnac G, Auradé F, Rochette-Egly C et al. (July 1998). "Retinoic acid receptors and muscle b-HLH proteins: partners in retinoid-induced myogenesis". Oncogene 16 (26): 3369–78. doi:10.1038/sj.onc.1201894. PMID 9692544. 
  22. ^ Kataoka Y, Matsumura I, Ezoe S, Nakata S, Takigawa E, Sato Y et al. (November 2003). "Reciprocal inhibition between MyoD and STAT3 in the regulation of growth and differentiation of myoblasts". J. Biol. Chem. 278 (45): 44178–87. doi:10.1074/jbc.M304884200. PMID 12947115. 
  23. ^ Maleki SJ, Royer CA, Hurlburt BK (June 1997). "MyoD-E12 heterodimers and MyoD-MyoD homodimers are equally stable". Biochemistry 36 (22): 6762–7. doi:10.1021/bi970262m. PMID 9184158. 
  24. ^ Micheli L, Leonardi L, Conti F, Buanne P, Canu N, Caruso M et al. (March 2005). "PC4 coactivates MyoD by relieving the histone deacetylase 4-mediated inhibition of myocyte enhancer factor 2C". Mol. Cell. Biol. 25 (6): 2242–59. doi:10.1128/MCB.25.6.2242-2259.2005. PMC 1061592. PMID 15743821. 
  25. ^ Micheli L, Leonardi L, Conti F, Maresca G, Colazingari S, Mattei E et al. (February 2011). "PC4/Tis7/IFRD1 stimulates skeletal muscle regeneration and is involved in myoblast differentiation as a regulator of MyoD and NF-kappaB". J. Biol. Chem. 286 (7): 5691–707. doi:10.1074/jbc.M110.162842. PMC 3037682. PMID 21127072. 

Further reading[edit]

External links[edit]