Document Detail


Merlin facilitates ubiquitination and degradation of transactivation-responsive RNA-binding protein.
MedLine Citation:
PMID:  16247459     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Nf2 tumor suppressor codes for merlin, a protein whose function is largely unknown. We have previously demonstrated a novel interaction between merlin and TRBP, which inhibits the oncogenic activity of TRBP. In spite of the significance of their functional interaction, its molecular mechanism still remains to be elucidated. In this report, we investigated how merlin inhibits the oncogenic activity of TRBP in association with cell growth conditions. In the human embryonic kidney 293 cell line, the level of endogenous merlin increased, whereas that of endogenous TRBP significantly decreased along with the increase in cell confluence. We demonstrated that the carboxyl-terminal region of TRBP was responsible for this phenomenon using stable cell lines expressing deletion mutants of TRBP. The overexpression of merlin decreased the protein level of TRBP, and the ubiquitin-like subdomain of merlin's FERM domain was important for this activity. We also demonstrated that TRBP is ubiquitinylated and the ubiquitinylated forms of TRBP are accumulated by ectopically expressed merlin or cell confluence in the presence of MG132, a proteasome inhibitor. Furthermore, we showed that the regulation of TRBP in response to cell confluence was abolished upon knockdown of merlin expression by specific small interfering RNA. Finally, we showed that ectopically expressed merlin restored cell-cell contact inhibition in cells stably expressing TRBP but not in TRBPDeltac. These results suggest that merlin is involved in the regulation of TRBP protein level by facilitating its ubiquitination in response to such cues as cell-cell contacts.
Authors:
J Y Lee; H J Moon; W K Lee; H J Chun; C W Han; Y-W Jeon; Y Lim; Y H Kim; T-P Yao; K-H Lee; T-Y Jun; H K Rha; J-K Kang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  25     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-23     Completed Date:  2006-03-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  1143-52     Citation Subset:  IM    
Copyright Information:
Oncogene (2006) 25, 1143-1152. doi:10.1038/sj.onc.1209150; published online 10 October 2005.
Affiliation:
Catholic Neuroscience Center, The Catholic University of Korea, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cell Adhesion
Humans
Immunoprecipitation
Kidney / cytology,  metabolism
Leupeptins / pharmacology
Mice
NIH 3T3 Cells
Neurofibromin 2 / antagonists & inhibitors,  genetics,  metabolism*
RNA, Small Interfering / pharmacology
RNA-Binding Proteins / genetics,  metabolism*
Sequence Deletion
Transcriptional Activation
Transfection
Ubiquitin / metabolism*
Chemical
Reg. No./Substance:
0/Leupeptins; 0/Neurofibromin 2; 0/RNA, Small Interfering; 0/RNA-Binding Proteins; 0/Ubiquitin; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; 136628-24-5/trans-activation responsive RNA-binding protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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