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Updated: Dec 20, 2025
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Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
Published on: May 17, 2016
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MYC protein stability is negatively regulated by BRD4
Ballachanda N Devaiah1, Jie Mu1, Ben Akman1
1Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892.
Summary
Bromodomain protein 4 (BRD4) phosphorylates and degrades the protooncogene MYC. However, the MYC-stabilizing kinase ERK1 inhibits BRD4, revealing a complex regulatory feedback loop controlling MYC levels in cells.
Area of Science:
- Molecular Biology
- Cancer Biology
- Epigenetics
Background:
- The protooncogene MYC is crucial for cell proliferation and metabolism, and its dysregulation drives cancer.
- MYC protein stability is tightly controlled by phosphorylation at specific sites (Thr58 for degradation, Ser62 for stabilization).
- Bromodomain protein 4 (BRD4) is an epigenetic regulator that enhances transcription of protooncogenes, including MYC.
Purpose of the Study:
- To investigate the role of BRD4 in regulating MYC protein levels and activity.
- To elucidate the interplay between BRD4, MYC, and the kinase ERK1 in controlling cellular processes.
Main Methods:
- Phosphorylation assays to determine BRD4's effect on MYC.
- Ubiquitination and degradation studies.
- Chromatin immunoprecipitation (ChIP) to assess BRD4-mediated chromatin remodeling.
- Kinase activity assays for BRD4 and ERK1.
Main Results:
- BRD4 directly phosphorylates MYC at Thr58, promoting its ubiquitination and subsequent degradation.
- BRD4 degradation, not just inhibition, leads to increased MYC protein levels.
- MYC inhibits the histone acetyltransferase (HAT) activity of BRD4, suggesting a feedback mechanism for MYC autoregulation.
- The MYC-stabilizing kinase ERK1 inhibits BRD4's kinase activity, thereby indirectly stabilizing MYC.
Conclusions:
- BRD4 acts as a negative regulator of MYC protein levels through phosphorylation-induced degradation.
- MYC autoregulates its own transcription by inhibiting BRD4's chromatin remodeling activity at its locus.
- ERK1 counteracts BRD4's inhibitory effect on MYC by inhibiting BRD4 kinase activity, highlighting a complex regulatory network.
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