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Updated: Aug 24, 2026

Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
Merlin, a tumor suppressor, interacts with transactivation-responsive RNA-binding protein and inhibits its oncogenic
Joo Yong Lee1, Hongtae Kim, Chung Hun Ryu
1Catholic Neuroscience Center, The Catholic University of Korea, Seoul 137-701, Korea.
Abstract:
The neurofibromatosis type 2 gene-encoded protein, merlin, is related to the ERM (ezrin, radixin, and moesin) family of membrane-cytoskeleton-associated proteins. Recent studies suggest that the loss of neurofibromatosis type 2 function contributes to tumor development and metastasis. Although the cellular functions of merlin as a tumor suppressor are relatively well characterized, the cellular mechanism whereby merlin controls cell proliferation from membrane locations is still poorly understood. During our efforts to find potential merlin modulators through protein-protein interactions, we identified transactivation-responsive RNA-binding protein (TRBP) as a merlin-binding protein in a yeast two-hybrid screen. The interaction between TRBP and merlin was confirmed by glutathione S-transferase pull-down assays, co-immunoprecipitation, and co-localization experiments. The carboxyl-terminal regions of each protein were responsible for their interaction. Cells overexpressing TRBP showed enhanced cell growth in cell proliferation assays and also exhibited transformed phenotypes, such as anchorage-independent cell growth and tumor development in mouse xenografts. Merlin efficiently inhibited these oncogenic activities of TRBP in our experiments. These results provide the first clue to the functional interaction between TRBP and merlin and suggest a novel mechanism for the tumor suppressor function of merlin both in vitro and in vivo.
Insights
Neurofibromatosis type 2 protein (merlin) interacts with transactivation-responsive RNA-binding protein (TRBP). Merlin suppresses TRBP
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Merlin, encoded by the neurofibromatosis type 2 gene, is a tumor suppressor related to ERM proteins.
- Loss of merlin function is linked to tumor development and metastasis.
- The precise mechanism of merlin's control over cell proliferation is not fully understood.
Purpose of the Study:
- To identify merlin-binding proteins and elucidate their functional interaction.
- To investigate the role of merlin in regulating the oncogenic activities of its binding partners.
- To explore a novel mechanism for merlin's tumor suppressor function.
Main Methods:
- Yeast two-hybrid screening to identify merlin-interacting proteins.
- Biochemical validation including glutathione S-transferase pull-down and co-immunoprecipitation assays.
- Cellular assays for proliferation, anchorage-independent growth, and in vivo tumor development in mouse xenografts.
Main Results:
- Transactivation-responsive RNA-binding protein (TRBP) was identified as a merlin-binding protein.
- The carboxyl-terminal regions of both merlin and TRBP mediate their interaction.
- Overexpression of TRBP enhanced cell growth and induced transformed phenotypes, which were suppressed by merlin.
Conclusions:
- This study reveals a functional interaction between merlin and TRBP.
- Merlin inhibits the oncogenic activities of TRBP, suggesting a novel tumor suppressor mechanism.
- The findings provide insights into merlin's role in controlling cell proliferation and tumor development.
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