Understanding the Role of Intrinsically Disordered Proteins (IDPs) in Cancer Biology Workshop

Intrinsically disordered proteins (IDPs), which lack a conventional ordered structure, are involved in many fundamental cellular processes such as splicing, signaling, and transcriptional regulation. The dysregulation of IDPs has been connected to many human diseases, including cancer. The oncogenic transcription factor c-Myc is a prominent example of an IDP that affects cell growth, apoptosis, and metabolic processes.

IDPs interact through high-specificity/low-affinity binding sites with other proteins in protein networks. IDPs' structural information to understand the functions of the proteins and their protein interaction networks is instrumental for progress in cancer biology, especially for therapeutics development.

Despite advancements, structural information of disordered proteins still presents a significant obstacle due to remarkable conformational flexibility and plasticity. Therefore, developing new technologies and methods that investigate IDPs' structural dynamics and interaction with binding partners is valuable. Recent progress in cryo-electron microscopy (cryoEM), nuclear magnetic resonance (NMR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, single-molecule FRET, and microscopy-based technologies can offer alternatives to unravel the structure and dynamics of IDPs.

Besides, accurate prediction of IDP structures through computational approaches, e.g., the recently developed AI program AlphaFold, can also be valuable. These technological advancements in understanding IDPs will help generate new research opportunities and cross-disciplinary collaborations that pave the way for characterizing their links to disease phenotypes, especially cancer.

To examine the role of IDPs in cancer biology, NCI held a virtual workshop on Sept. 26, 2022. Experts in the field illustrated how technological advancements enlighten cell biological investigations of IDPs during the meeting.

Documents from the Workshop

• Agenda 
• List of Speakers and Moderators

Workshop Report

A perspective on cutting-edge approaches to address challenges in the field of intrinsically disordered proteins (with a focus on cancer biology) based on discussions at the meeting was published in Trends in Biochemical Sciences: Dissecting the biophysics and biology of intrinsically disordered proteins

DCB Contacts for the Workshop

For additional information about the workshop, please contact Dr. Anowarul Amin (anowarul.amin@nih.gov) or Dr. Stefan Maas (stefan.maas@nih.gov).