Merlin, a tumor suppressor, interacts with transactivation-responsive RNA-binding protein and inhibits its oncogenic activity.
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.
Lee
Joo Yong
JY
Catholic Neuroscience Center, The Catholic University of Korea, Seoul 137-701, Korea.
Kim
Hongtae
H
Ryu
Chung Hun
CH
Kim
Jae Young
JY
Choi
Byung Hyune
BH
Lim
Young
Y
Huh
Pil-Woo
PW
Kim
Young-Hoon
YH
Lee
Kweon-Haeng
KH
Jun
Tae-Youn
TY
Rha
Hyung Kyun
HK
Kang
Joon-Ki
JK
Choi
Chang Rak
CR
D000362:Agar / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D025581:Neurofibromin 2 / Q000378:metabolism / Q000502:physiology*; D009857:Oncogenes; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000099253:Trans-Activation Responsive RNA-Binding Protein
D000362:Agar; D018076:DNA, Complementary; D005982:Glutathione Transferase; D025581:Neurofibromin 2; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D000099253:Trans-Activation Responsive RNA-Binding Protein