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The N-Myc MB0-MBI region interacts specifically and dynamically with the N-lobe of Aurora kinase A

Hultman, Johanna ; Morad, Vivian ; Tanner, Eliane ; Kenney, Tristan M.G. ; Pietras, Zuzanna ; Khare, Lalit Pramod ; Derbyshire, Dean ; Resetca, Diana ; Arrowsmith, Cheryl H. and Aili, Daniel , et al. (2026) In Nature Communications 17(1).
Abstract

The intrinsically disordered MYC proteins are master regulators of cellular growth and function, but when deregulated they become cancer drivers. MYC-protein interactions are key to oncogenesis, and while disrupting such interactions would be of significant therapeutic benefit, the intrinsically disordered properties of MYC have dramatically hampered their characterization. Here, we apply an integrated structural biology approach to describe the structure and dynamics of the N-Myc–Aurora A complex, which is critical in neuroendocrine tumor progression. We reveal a functional interaction where multiple binding sites on N-Myc interact with the Aurora A N-lobe. The interaction is governed by aromatic clusters within the conserved MB0 and... (More)

The intrinsically disordered MYC proteins are master regulators of cellular growth and function, but when deregulated they become cancer drivers. MYC-protein interactions are key to oncogenesis, and while disrupting such interactions would be of significant therapeutic benefit, the intrinsically disordered properties of MYC have dramatically hampered their characterization. Here, we apply an integrated structural biology approach to describe the structure and dynamics of the N-Myc–Aurora A complex, which is critical in neuroendocrine tumor progression. We reveal a functional interaction where multiple binding sites on N-Myc interact with the Aurora A N-lobe. The interaction is governed by aromatic clusters within the conserved MB0 and MBI motifs in N-Myc that interact with Aurora A in a dynamic binding mode that allosterically promotes kinase activation. We show that N-Myc binding to the Aurora A N-lobe can be inhibited by the small-molecule AurkinA, providing opportunity for therapeutical strategies to disrupt this interaction.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
17
issue
1
article number
2016
publisher
Nature Publishing Group
external identifiers
  • scopus:105031085986
  • pmid:41735282
ISSN
2041-1723
DOI
10.1038/s41467-026-69725-1
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2026.
id
ca21a383-9261-4471-b265-5931a79890e4
date added to LUP
2026-04-07 13:53:15
date last changed
2026-06-02 20:21:18
@article{ca21a383-9261-4471-b265-5931a79890e4,
  abstract     = {{<p>The intrinsically disordered MYC proteins are master regulators of cellular growth and function, but when deregulated they become cancer drivers. MYC-protein interactions are key to oncogenesis, and while disrupting such interactions would be of significant therapeutic benefit, the intrinsically disordered properties of MYC have dramatically hampered their characterization. Here, we apply an integrated structural biology approach to describe the structure and dynamics of the N-Myc–Aurora A complex, which is critical in neuroendocrine tumor progression. We reveal a functional interaction where multiple binding sites on N-Myc interact with the Aurora A N-lobe. The interaction is governed by aromatic clusters within the conserved MB0 and MBI motifs in N-Myc that interact with Aurora A in a dynamic binding mode that allosterically promotes kinase activation. We show that N-Myc binding to the Aurora A N-lobe can be inhibited by the small-molecule AurkinA, providing opportunity for therapeutical strategies to disrupt this interaction.</p>}},
  author       = {{Hultman, Johanna and Morad, Vivian and Tanner, Eliane and Kenney, Tristan M.G. and Pietras, Zuzanna and Khare, Lalit Pramod and Derbyshire, Dean and Resetca, Diana and Arrowsmith, Cheryl H. and Aili, Daniel and Ekström, Simon and Penn, Linda Z. and Wallner, Björn and Ahlner, Alexandra and Sunnerhagen, Maria}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{The N-Myc MB0-MBI region interacts specifically and dynamically with the N-lobe of Aurora kinase A}},
  url          = {{http://dx.doi.org/10.1038/s41467-026-69725-1}},
  doi          = {{10.1038/s41467-026-69725-1}},
  volume       = {{17}},
  year         = {{2026}},
}