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Published on: April 29, 2011
Functional antagonism between c-Jun and MyoD proteins: a direct physical association
E Bengal1, L Ransone, R Scharfmann
1Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186-5800.
Abstract:
The product of the proto-oncogene Jun inhibits myogenesis. Constitutive expression of Jun in myoblasts interferes with the expression and the function of MyoD protein. In transient transfection assays Jun inhibits transactivation of the MyoD promoter, the muscle creatine kinase enhancer, and a reporter gene linked to MyoD DNA-binding sites. Conversely, MyoD suppresses the transactivation by Jun of genes linked to an AP-1 site. We demonstrate that both in vivo and in vitro MyoD and Jun proteins physically interact. Mutational analysis suggests that this interaction occurs via the leucine zipper domain of Jun and the helix-loop-helix region of MyoD.
Insights
The proto-oncogene Jun protein inhibits muscle development by interfering with the MyoD protein. MyoD and Jun physically interact, impacting gene regulation in myogenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncogenes
Background:
- The proto-oncogene Jun is a transcription factor involved in various cellular processes.
- Myogenic Differentiation 1 (MyoD) is a key transcription factor regulating muscle development.
- The interplay between Jun and MyoD in myogenesis is not fully understood.
Purpose of the Study:
- To investigate the inhibitory role of Jun on myogenesis.
- To elucidate the molecular mechanisms underlying the interaction between Jun and MyoD.
- To determine how Jun affects MyoD function and gene expression.
Main Methods:
- Transient transfection assays to assess promoter and enhancer activity.
- Analysis of reporter gene expression linked to MyoD and AP-1 binding sites.
- In vivo and in vitro co-immunoprecipitation to detect protein-protein interactions.
- Mutational analysis of Jun and MyoD interaction domains.
Main Results:
- Constitutive expression of Jun inhibits myogenesis by interfering with MyoD.
- Jun suppresses the transactivation of MyoD-regulated promoters and enhancers.
- MyoD antagonizes Jun-mediated transactivation of AP-1 site-linked genes.
- Physical interaction between MyoD and Jun proteins was confirmed both in vivo and in vitro.
- The interaction involves Jun's leucine zipper domain and MyoD's helix-loop-helix region.
Conclusions:
- The proto-oncogene Jun inhibits myogenesis through direct physical interaction with the MyoD protein.
- This interaction modulates the transcriptional activity of both proteins, affecting muscle cell differentiation.
- Understanding the Jun-MyoD interaction provides insights into the regulation of muscle development and potential oncogenic pathways.
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