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Updated: Aug 13, 2026

RhoC GTPase Activation Assay
Published on: August 22, 2010
The TC21 oncoprotein interacts with the Ral guanosine nucleotide dissociation factor
M López-Barahona1, X R Bustelo, M Barbacid
1Department of Molecular Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Abstract:
TC21 is a highly oncogenic member of the Ras superfamily of small GTP binding proteins. We have used the yeast two hybrid system to identify proteins that interact with an oncogenic form of the TC21 protein. cDNA clones encoding the carboxy-terminal region of the RalGDS protein were isolated from human B-cell and HeLa cDNA libraries. RalGDS is an exchange factor that stimulates GDP dissociation from Ral, another member of the Ras superfamily of proteins. The interaction between RalGDS to TC21 is direct and appears to be mediated by the effector domain of TC21 and the carboxy-terminal region of RalGDS. Moreover, RalGDS only binds to TC21 in its active, GTP-loaded configuration. These results suggest that RalGDS might be an effector molecule for TC21 and may participate in cross-talking between Ral and TC21 signalling pathways.
Insights
Researchers identified Ral Guanine nucleotide Dissociation Stimulator (RalGDS) as a direct binding partner for the oncogenic TC21 protein. This interaction suggests RalGDS may act as an effector for TC21, potentially linking TC21 and Ral signaling pathways.
Area of Science:
- Molecular Biology
- Oncology
- Cell Signaling
Background:
- TC21 is a potent oncogenic protein within the Ras superfamily.
- Understanding TC21's interactions is crucial for deciphering its role in cancer.
Purpose of the Study:
- To identify proteins interacting with an oncogenic form of TC21.
- To elucidate the molecular mechanism and pathway involvement of TC21 interactions.
Main Methods:
- Yeast two-hybrid system for protein interaction screening.
- Isolation of cDNA clones encoding RalGDS from human cell lines.
Main Results:
- Identified RalGDS as a direct binding partner for TC21.
- Interaction is mediated by TC21's effector domain and RalGDS's C-terminal region.
- RalGDS binding is specific to the active, GTP-bound state of TC21.
Conclusions:
- RalGDS is a potential effector molecule for TC21.
- This interaction may mediate cross-talk between TC21 and Ral signaling pathways.
- Findings contribute to understanding oncogenic Ras superfamily signaling.
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