Related Experiment Video
Updated: Feb 14, 2026
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
Targeting the Architecture of Deregulated Protein Complexes in Cancer
Eduard Stefan1, Jakob Troppmair2, Klaus Bister1
1Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Abstract:
The architectures of central signaling hubs are precisely organized by static and dynamic protein-protein interactions (PPIs). Upon deregulation, these PPI platforms are capable to propagate or initiate pathophysiological signaling events. This causes the acquisition of molecular features contributing to the etiology or progression of many diseases, including cancer, where deregulated molecular interactions of signaling proteins have been best studied. The reasons for PPI-dependent reprogramming of cancer-initiating cells are manifold; in many cases, mutations perturb PPIs, enzyme activities, protein abundance, or protein localization. Consequently, the pharmaceutical targeting of PPIs promises to be of remarkable therapeutic value. For this review we have selected three key players of oncogenic signaling which are differently affected by PPI deregulation: two (the small G proteins of the RAS family and the transcription factor MYC) are considered "undruggable" using classical drug discovery approaches and in the case of the third protein discussed here, PKA, standard kinase inhibitors, may be unsuitable in the clinic. These circumstances require alternative strategies, which may lie in pharmaceutical drug interference of critical PPIs accountable for oncogenic signaling.
Insights
Protein-protein interactions (PPIs) are crucial for cell signaling and disease progression. Targeting these interactions offers a promising therapeutic strategy for diseases like cancer, especially for previously "undruggable" targets.
Area of Science:
- Molecular Biology
- Biochemistry
- Oncology
Background:
- Cellular signaling hubs rely on precise protein-protein interactions (PPIs).
- Deregulation of these PPIs can initiate or propagate disease, notably cancer.
- Signaling protein interactions are fundamental to cancer etiology and progression.
Purpose of the Study:
- To review the role of PPI deregulation in oncogenic signaling.
- To highlight the therapeutic potential of targeting PPIs.
- To discuss challenges and alternative strategies for targeting key oncogenic proteins like RAS, MYC, and PKA.
Main Methods:
- Review of existing literature on protein-protein interactions in cancer signaling.
- Analysis of the impact of PPI deregulation on specific oncogenic proteins (RAS, MYC, PKA).
- Discussion of pharmaceutical strategies for targeting PPIs.
Main Results:
- PPIs are critical for the function of key oncogenic signaling proteins.
- Mutations, altered enzyme activity, protein abundance, or localization can disrupt PPIs in cancer.
- RAS and MYC are considered "undruggable" by conventional methods, and PKA requires alternative inhibition strategies.
Conclusions:
- Targeting PPIs presents a significant therapeutic opportunity in oncology.
- Alternative strategies are needed to address PPI deregulation for challenging targets like RAS, MYC, and PKA.
- Interfering with critical PPIs can offer a novel approach to treating cancer.
More Related Videos
10:01Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies
Published on: November 28, 2017
07:48Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
Related Concept Videos
01:57Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
01:57Protein Complexes with Interchangeable Parts
02:41Protein Complex Assembly
Many viruses self-assemble into a fully functional unit using the infected host cell to...
02:41Protein Complex Assembly
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:14Polymer Classification: Architecture