ArticleThe Biochemical journal2025
Aurora A binds to the transactivation domain of c-Myc and recognizes the phosphorylated N-terminal degron motif.
Article in The Biochemical journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- c-Myc: an emerging participant in heart failure.Frontiers in cardiovascular medicine · 2026Review
- The Yin-Yang balance of SIRT1 and SIRT2 in cancer metabolic remodeling.International journal of biological sciences · 2026Review
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Authors and funding
8 authors.
Funding
Abstract
The oncoprotein c-Myc is overexpressed or mutated in a large fraction of human cancers. The stability of c-Myc is controlled by phosphorylation of T58 and S62 within a conserved degron motif in the N-terminal transactivation domain, which triggers recruitment of the SCF ubiquitin ligase. The kinase Aurora A (AurA) has been shown to bind to both c-Myc and its paralog N-Myc and to promote their stability by interfering with ubiquitination and degradation. Here we show, using NMR and FRET experiments, that AurA binds to c-Myc through several discrete interactions spanning 145 residues within its transactivation domain. AurA binding to c-Myc is enhanced by phosphorylation of the T58/S62 degron, demonstrating that the kinase recognizes the pool of c-Myc that has been marked for degradation by the ubiquitin proteasome pathway. Although AurA binds to segments of c-Myc flanking the degron, it does not appear to form extensive interactions with the phosphorylated degron itself, potentially leaving it accessible on the AurA surface. These observations establish a foundation for understanding the role of AurA in regulating c-Myc ubiquitination and degradation.
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