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Published on: May 15, 2019
Crotonylation impedes c-Myc oncogenic activity
Nicholas J Wallbillich1,2, Peng Liao1,2, Rashmi Srivastava1,2
1Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112.
Summary
Crotonylation, a modification of the oncoprotein c-Myc, impairs its cancer-driving activity. Specific mutations in c-Myc enhance its oncogenic functions by altering interactions with its regulator Skp2.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- c-Myc is a crucial oncoprotein regulated by posttranslational modifications.
- Understanding these modifications is key to comprehending c-Myc's role in cancer.
Purpose of the Study:
- To investigate c-Myc crotonylation, a novel posttranslational modification.
- To determine the functional impact of c-Myc crotonylation on its oncogenic activity.
Main Methods:
- Biochemical analyses and high-resolution mass spectrometry were employed.
- Site-directed mutagenesis of identified crotonylation sites was performed.
- Interactions between c-Myc and Skp2 were assessed.
Main Results:
- c-Myc was found to be crotonylated at multiple lysine residues.
- Mutations at K289 and K298 enhanced cell proliferation and c-Myc binding to Skp2.
- The K298N mutation, found in human tumors, exhibited increased oncogenic activity.
- Crotonylation impairs c-Myc's oncogenic activity by modulating Skp2 interaction.
Conclusions:
- Crotonylation is a regulatory mechanism for c-Myc.
- This modification can attenuate c-Myc's oncogenic potential.
- Targeting c-Myc crotonylation may offer therapeutic strategies in cancer treatment.
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