title: The oncogenic fusion protein Pax3-FKHR has a greater post-translational stability relative to Pax3 during early myogenesis.
abstract: The childhood solid muscle tumor Alveolar Rhabdomyosarcoma (ARMS) is characterized by the t(2;13)(q35;q14) chromosomal translocation, which results in the fusion of two transcription factors important for myogenesis, Pax3 and FKHR (FOX01a). The effects of myogenic differentiation on the stability of FKHR have been well characterized. However, similar studies have yet to be performed on Pax3 or the oncogenic fusion protein Pax3-FKHR. Therefore, we demonstrate in the physiologically relevant mouse primary myoblast system that the expression of Pax3 decreases nearly 95% during the first 24 h of myogenic differentiation. In contrast, there is an aberrant persistence of expression of Pax3-FKHR during this same time period. These differences in protein expression levels do not result from changes on the transcriptional nor the translational level since we observed no concomitant decrease in the levels of Pax3 or Pax3-FKHR mRNA or in the ability of both proteins to be translated. Instead, a pulse-chase analysis determined that Pax3-FKHR has a half-life significantly greater than\ the half-life of wild type Pax3 demonstrating for the first time that Pax3-FKHR has greater post-translational protein stability relative to wild type Pax3 during early myogenic differentiation. Finally, the persistence of expression of Pax3-FKHR prevents the terminal differentiation of primary myoblasts demonstrating a biological consequence of its aberrant expression.
authors: Department of Genetics, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans, LA 70112, USA.
authors: Patrick J
authors: PJ
authors: Miller
authors: Andrew D
authors: AD
authors: Hollenbach
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008858:Microscopy, Phase-Contrast; D024510:Muscle Development / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis*; D046188:Protein Modification, Translational
chemical_list: D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; C523321:PAX3-FKHR fusion protein, human; D051761:Paired Box Transcription Factors; C068686:Pax3 protein, mouse
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