Cancer’s Spaghetti Proteins: Understanding Complex Biomarkers
Unraveling the MYC-AURKA Interaction: A New Frontier in Cancer Therapy
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c-MYC, a transcription factor implicated in over 70% of human cancers, has long been a target for cancer therapies. However, its intrinsically disordered nature has presented meaningful challenges. Now, researcher Dr. dunleavy is shedding light on a crucial interaction that stabilizes c-MYC – its binding with Aurora kinase A (AURKA) – potentially opening new avenues for drug growth.
The MYC-AURKA Connection: A Stabilizing Force in Cancer
AURKA, a known binding partner of c-MYC, appears to prevent the protein’s natural degradation. While this stabilization is established, the how remains a mystery.Understanding the precise structural and mechanistic details of this interaction is critical for designing effective inhibitors that can disrupt it, restoring normal protein turnover and potentially halting cancer progression.
The body naturally regulates protein levels through ubiquitination, a process where the protein ubiquitin tags proteins like c-MYC for degradation. AURKA’s influence on this process is central to Dunleavy’s research. “The hypothesis is that (when AURKA binds to c-MYC), the bound complex can’t be properly ubiquitinated nor sent for proper degradation of the protein,” Dunleavy explains. This suggests AURKA doesn’t directly modify c-MYC, but rather shields it from the body’s natural quality control mechanisms. This is a departure from typical kinase behavior, making the research especially compelling.
Cutting-Edge Biophysical Techniques reveal the Interaction
Dunleavy’s research employs a suite of advanced biophysical techniques to dissect the c-MYC-AURKA interaction. These include:
Continuous-wave electron paramagnetic resonance (CW-EPR): This technique tracks protein movement in real-time, providing insights into the dynamics of the complex.
X-ray crystallography and cryo-electron microscopy (cryo-EM): These methods are used to map the 3D structure of the c-MYC-AURKA complex, revealing how the interaction physically prevents c-MYC degradation.
* Ubiquitination assays: These assays directly measure how AURKA alters c-MYC’s modification with ubiquitin,confirming its impact on the degradation pathway.By combining these approaches, Dunleavy aims to build a extensive understanding of the mechanisms by which AURKA stabilizes c-MYC and interferes with its degradation. This detailed understanding is crucial for identifying potential vulnerabilities that can be exploited by new therapies.
Overcoming the “Undruggable” challenge of Intrinsically Disordered Proteins
c-MYC’s classification as an intrinsically disordered protein (IDP) has historically hindered drug development.IDPs lack the well-defined binding pockets that traditional drugs target. However, Dunleavy’s work suggests that even these “undruggable” proteins can be viable targets.
“What I find so cool about this story is that it is not a traditional kinase story,” Dunleavy states. Her research focuses on defining the structure of the MYC-AURKA complexes and how ubiquitination alters their interaction. This work will create a “structural and mechanistic roadmap” for future drug design efforts.
The broader implications of this research extend to understanding the stabilization of c-MYC in various cancerous conditions. Currently, the precise mechanisms of this stabilization remain largely unknown, highlighting the importance of Dunleavy’s investigation.
A Commitment to Mentorship and Expanding Access to Science
Dunleavy’s dedication extends beyond the laboratory. As a first-generation college graduate, she is passionate about mentorship and increasing depiction in STEM fields. Receiving the MOSAIC award has empowered her to give back to the community, inspiring others from underrepresented backgrounds to pursue careers in research.
“I was drawn to the MOSAIC program since I have a passion for mentorship and helping the underrepresented…to show them that research exists,” she explains. She envisions herself as a resource for aspiring scientists, fostering a more inclusive and diverse research landscape. Her commitment to both scientific discovery and mentorship positions her as a rising leader in the field of cancer research.