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

Johanna Hultman1, Vivian Morad1, Eliane Tanner1

  • 1Department of Physics, Chemistry and Biology, Division of Chemistry, Linköping University, Linköping, Sweden.

Nature Communications
|February 24, 2026
PubMed

Insights

Intrinsically disordered MYC proteins drive cancer when deregulated. Researchers uncovered how N-Myc interacts with Aurora A, revealing a target for new cancer therapies.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Oncology

Background:

  • MYC proteins are crucial for cell growth but drive cancer when deregulated.
  • The disordered nature of MYC proteins complicates the study of their interactions.
  • Understanding MYC-Aurora A interactions is vital for neuroendocrine tumor progression.

Purpose of the Study:

  • To elucidate the structure and dynamics of the N-Myc-Aurora A complex.
  • To identify the molecular mechanisms underlying their functional interaction.
  • To explore therapeutic strategies targeting this interaction.

Main Methods:

  • Integrated structural biology techniques.
  • Analysis of protein-protein binding sites.
  • Small-molecule inhibition assays.

Main Results:

  • Detailed description of the N-Myc-Aurora A complex structure and dynamics.
  • Identification of multiple binding sites on N-Myc interacting with Aurora A's N-lobe.
  • Aromatic clusters in N-Myc motifs mediate a dynamic binding mode that activates Aurora A kinase.
  • The small molecule AurkinA inhibits N-Myc binding to Aurora A.

Conclusions:

  • The N-Myc-Aurora A interaction is a key driver in neuroendocrine tumors.
  • Disrupting this interaction via small molecules like AurkinA offers a potential therapeutic avenue.
  • This study provides a structural basis for developing targeted cancer therapies.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.8K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
8.8K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.7K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.5K
Attachment of Sister Chromatids02:57

Attachment of Sister Chromatids

As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules.  Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall...
4.1K