MyoD and E-protein heterodimers switch rhabdomyosarcoma cells from an arrested myoblast phase to a differentiated state

FieldValue
dc.contributor.authorYang, Zhihong
dc.contributor.authorMacQuarrie, Kyle L.
dc.contributor.authorAnalau, Erwin
dc.contributor.authorTyler, Ashlee E.
dc.contributor.authorDilworth, Francis Jeffrey
dc.contributor.authorCao, Yi
dc.contributor.authorDiede, Scott J.
dc.contributor.authorTapscott, Stephen J.
dc.date.accessioned2010-11-05T13:40:36Z
dc.date.available2010-11-05T13:40:36Z
dc.date.created2009
dc.date.issued2009
dc.identifier.citationGenes & Development, 23, 694-707.
dc.identifier.urihttp://hdl.handle.net/10393/19666
dc.description.abstractRhabdomyosarcomas are characterized by expression of myogenic specification genes, such as MyoD and/or Myf5, and some muscle structural genes in a population of cells that continues to replicate. Because MyoD is sufficient to induce terminal differentiation in a variety of cell types, we have sought to determine the molecular mechanisms that prevent MyoD activity in human embryonal rhabdomyosarcoma cells. In this study, we show that a combination of inhibitory Musculin:E-protein complexes and a novel splice form of E2A compete with MyoD for the generation of active full-length E-protein:MyoD heterodimers. A forced heterodimer between MyoD and the full-length E12 robustly restores differentiation in rhabdomyosarcoma cells and broadly suppresses multiple inhibitory pathways. Our studies indicate that rhabdomyosarcomas represent an arrested progress through a normal transitional state that is regulated by the relative abundance of heterodimers between MyoD and the full-length E2A proteins. The demonstration that multiple inhibitory mechanisms can be suppressed and myogenic differentiation can be induced in the RD rhabdomyosarcomas by increasing the abundance of MyoD:E-protein heterodimers suggests a central integrating function that can be targeted to force differentiation in muscle cancer cells.
dc.language.isoen
dc.subjectE2A
dc.subjectMusculin
dc.subjectMyoD
dc.subjectmyogenesis
dc.subjectrhabdomyosarcoma
dc.titleMyoD and E-protein heterodimers switch rhabdomyosarcoma cells from an arrested myoblast phase to a differentiated state
dc.typeArticle
dc.identifier.doi10.1101/gad.1765109
CollectionM├ędecine cellulaire et mol├ęculaire // Cellular and Molecular Medicine

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