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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Jan;93(1):5–9. doi: 10.1172/JCI116982

Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic transcription factors.

G Anand 1, D N Shapiro 1, P S Dickman 1, E V Prochownik 1
PMCID: PMC293710  PMID: 8282820

Abstract

Skeletal myogenesis is regulated by a group of transcription factors (MyoD, myogenin, myf5, and myf6) that are "basic helix-loop-helix" proteins that bind to the promoters of muscle-specific genes and promote their expression. We have previously shown that after a mutation of Leu122 to Arg the DNA binding basic domain of MyoD confers c-myc-like functional characteristics to the protein. In this study we used single-strand conformation polymorphism analysis to determine whether such mutations occur naturally in rhabdomyosarcomas. We have found that the basic domains of all the myogenic factors remain unaltered in rhabdomyosarcomas. Selection against such mutations may be the result of functional redundancy of these myogenic transcription factors.

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Selected References

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  1. Ayer D. E., Kretzner L., Eisenman R. N. Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell. 1993 Jan 29;72(2):211–222. doi: 10.1016/0092-8674(93)90661-9. [DOI] [PubMed] [Google Scholar]
  2. Blackwell T. K., Weintraub H. Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection. Science. 1990 Nov 23;250(4984):1104–1110. doi: 10.1126/science.2174572. [DOI] [PubMed] [Google Scholar]
  3. Blackwood E. M., Eisenman R. N. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991 Mar 8;251(4998):1211–1217. doi: 10.1126/science.2006410. [DOI] [PubMed] [Google Scholar]
  4. Bober E., Lyons G. E., Braun T., Cossu G., Buckingham M., Arnold H. H. The muscle regulatory gene, Myf-6, has a biphasic pattern of expression during early mouse development. J Cell Biol. 1991 Jun;113(6):1255–1265. doi: 10.1083/jcb.113.6.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braun T., Bober E., Buschhausen-Denker G., Kohtz S., Grzeschik K. H., Arnold H. H., Kotz S. Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products. EMBO J. 1989 Dec 1;8(12):3617–3625. doi: 10.1002/j.1460-2075.1989.tb08535.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Braun T., Buschhausen-Denker G., Bober E., Tannich E., Arnold H. H. A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J. 1989 Mar;8(3):701–709. doi: 10.1002/j.1460-2075.1989.tb03429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Braun T., Rudnicki M. A., Arnold H. H., Jaenisch R. Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell. 1992 Oct 30;71(3):369–382. doi: 10.1016/0092-8674(92)90507-9. [DOI] [PubMed] [Google Scholar]
  8. Braun T., Winter B., Bober E., Arnold H. H. Transcriptional activation domain of the muscle-specific gene-regulatory protein myf5. Nature. 1990 Aug 16;346(6285):663–665. doi: 10.1038/346663a0. [DOI] [PubMed] [Google Scholar]
  9. Brennan T. J., Chakraborty T., Olson E. N. Mutagenesis of the myogenin basic region identifies an ancient protein motif critical for activation of myogenesis. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5675–5679. doi: 10.1073/pnas.88.13.5675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dang C. V., Dolde C., Gillison M. L., Kato G. J. Discrimination between related DNA sites by a single amino acid residue of Myc-related basic-helix-loop-helix proteins. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):599–602. doi: 10.1073/pnas.89.2.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davis R. L., Cheng P. F., Lassar A. B., Weintraub H. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell. 1990 Mar 9;60(5):733–746. doi: 10.1016/0092-8674(90)90088-v. [DOI] [PubMed] [Google Scholar]
  12. Douglass E. C., Valentine M., Etcubanas E., Parham D., Webber B. L., Houghton P. J., Houghton J. A., Green A. A. A specific chromosomal abnormality in rhabdomyosarcoma. Cytogenet Cell Genet. 1987;45(3-4):148–155. doi: 10.1159/000132446. [DOI] [PubMed] [Google Scholar]
  13. Emerson C. P. Myogenesis and developmental control genes. Curr Opin Cell Biol. 1990 Dec;2(6):1065–1075. doi: 10.1016/0955-0674(90)90157-a. [DOI] [PubMed] [Google Scholar]
  14. Falcone G., Tatò F., Alemà S. Distinctive effects of the viral oncogenes myc, erb, fps, and src on the differentiation program of quail myogenic cells. Proc Natl Acad Sci U S A. 1985 Jan;82(2):426–430. doi: 10.1073/pnas.82.2.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gregor P. D., Sawadogo M., Roeder R. G. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev. 1990 Oct;4(10):1730–1740. doi: 10.1101/gad.4.10.1730. [DOI] [PubMed] [Google Scholar]
  16. Hiti A. L., Bogenmann E., Gonzales F., Jones P. A. Expression of the MyoD1 muscle determination gene defines differentiation capability but not tumorigenicity of human rhabdomyosarcomas. Mol Cell Biol. 1989 Nov;9(11):4722–4730. doi: 10.1128/mcb.9.11.4722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kretzner L., Blackwood E. M., Eisenman R. N. Myc and Max proteins possess distinct transcriptional activities. Nature. 1992 Oct 1;359(6394):426–429. doi: 10.1038/359426a0. [DOI] [PubMed] [Google Scholar]
  18. Labrune P., Melle D., Rey F., Berthelon M., Caillaud C., Rey J., Munnich A., Lyonnet S. Single-strand conformation polymorphism for detection of mutations and base substitutions in phenylketonuria. Am J Hum Genet. 1991 Jun;48(6):1115–1120. [PMC free article] [PubMed] [Google Scholar]
  19. Lassar A. B., Davis R. L., Wright W. E., Kadesch T., Murre C., Voronova A., Baltimore D., Weintraub H. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991 Jul 26;66(2):305–315. doi: 10.1016/0092-8674(91)90620-e. [DOI] [PubMed] [Google Scholar]
  20. Littlewood T. D., Amati B., Land H., Evan G. I. Max and c-Myc/Max DNA-binding activities in cell extracts. Oncogene. 1992 Sep;7(9):1783–1792. [PubMed] [Google Scholar]
  21. Miner J. H., Wold B. J. c-myc inhibition of MyoD and myogenin-initiated myogenic differentiation. Mol Cell Biol. 1991 May;11(5):2842–2851. doi: 10.1128/mcb.11.5.2842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Orita M., Iwahana H., Kanazawa H., Hayashi K., Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2766–2770. doi: 10.1073/pnas.86.8.2766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. PATTON R. B., HORN R. C., Jr Rhabdomyosarcoma: clinical and pathological features and comparison with human fetal and embryonal skeletal muscle. Surgery. 1962 Oct;52:572–584. [PubMed] [Google Scholar]
  24. Prendergast G. C., Lawe D., Ziff E. B. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell. 1991 May 3;65(3):395–407. doi: 10.1016/0092-8674(91)90457-a. [DOI] [PubMed] [Google Scholar]
  25. Prochownik E. V., VanAntwerp M. E. Differential patterns of DNA binding by myc and max proteins. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):960–964. doi: 10.1073/pnas.90.3.960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ptácek L. J., George A. L., Jr, Griggs R. C., Tawil R., Kallen R. G., Barchi R. L., Robertson M., Leppert M. F. Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell. 1991 Nov 29;67(5):1021–1027. doi: 10.1016/0092-8674(91)90374-8. [DOI] [PubMed] [Google Scholar]
  27. Rudnicki M. A., Braun T., Hinuma S., Jaenisch R. Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell. 1992 Oct 30;71(3):383–390. doi: 10.1016/0092-8674(92)90508-a. [DOI] [PubMed] [Google Scholar]
  28. Sassoon D., Lyons G., Wright W. E., Lin V., Lassar A., Weintraub H., Buckingham M. Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature. 1989 Sep 28;341(6240):303–307. doi: 10.1038/341303a0. [DOI] [PubMed] [Google Scholar]
  29. Schneider M. D., Perryman M. B., Payne P. A., Spizz G., Roberts R., Olson E. N. Autonomous expression of c-myc in BC3H1 cells partially inhibits but does not prevent myogenic differentiation. Mol Cell Biol. 1987 May;7(5):1973–1977. doi: 10.1128/mcb.7.5.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sorrentino V., Pepperkok R., Davis R. L., Ansorge W., Philipson L. Cell proliferation inhibited by MyoD1 independently of myogenic differentiation. Nature. 1990 Jun 28;345(6278):813–815. doi: 10.1038/345813a0. [DOI] [PubMed] [Google Scholar]
  31. Tapscott S. J., Davis R. L., Thayer M. J., Cheng P. F., Weintraub H., Lassar A. B. MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science. 1988 Oct 21;242(4877):405–411. doi: 10.1126/science.3175662. [DOI] [PubMed] [Google Scholar]
  32. Tapscott S. J., Thayer M. J., Weintraub H. Deficiency in rhabdomyosarcomas of a factor required for MyoD activity and myogenesis. Science. 1993 Mar 5;259(5100):1450–1453. doi: 10.1126/science.8383879. [DOI] [PubMed] [Google Scholar]
  33. Trent J., Casper J., Meltzer P., Thompson F., Fogh J. Nonrandom chromosome alterations in rhabdomyosarcoma. Cancer Genet Cytogenet. 1985 Apr 1;16(3):189–197. doi: 10.1016/0165-4608(85)90045-7. [DOI] [PubMed] [Google Scholar]
  34. Van Antwerp M. E., Chen D. G., Chang C., Prochownik E. V. A point mutation in the MyoD basic domain imparts c-Myc-like properties. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9010–9014. doi: 10.1073/pnas.89.19.9010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weintraub H., Davis R., Tapscott S., Thayer M., Krause M., Benezra R., Blackwell T. K., Turner D., Rupp R., Hollenberg S. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991 Feb 15;251(4995):761–766. doi: 10.1126/science.1846704. [DOI] [PubMed] [Google Scholar]
  36. Whang-Peng J., Knutsen T., Theil K., Horowitz M. E., Triche T. Cytogenetic studies in subgroups of rhabdomyosarcoma. Genes Chromosomes Cancer. 1992 Nov;5(4):299–310. doi: 10.1002/gcc.2870050405. [DOI] [PubMed] [Google Scholar]
  37. Winter B., Braun T., Arnold H. H. Co-operativity of functional domains in the muscle-specific transcription factor Myf-5. EMBO J. 1992 May;11(5):1843–1855. doi: 10.1002/j.1460-2075.1992.tb05236.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wright W. E. Muscle basic helix-loop-helix proteins and the regulation of myogenesis. Curr Opin Genet Dev. 1992 Apr;2(2):243–248. doi: 10.1016/s0959-437x(05)80280-1. [DOI] [PubMed] [Google Scholar]
  39. Yutzey K. E., Rhodes S. J., Konieczny S. F. Differential trans activation associated with the muscle regulatory factors MyoD1, myogenin, and MRF4. Mol Cell Biol. 1990 Aug;10(8):3934–3944. doi: 10.1128/mcb.10.8.3934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zervos A. S., Gyuris J., Brent R. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell. 1993 Jan 29;72(2):223–232. doi: 10.1016/0092-8674(93)90662-a. [DOI] [PubMed] [Google Scholar]

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