Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein.

Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein. Research Abstract Details 

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Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein. Abstract Text:

Hansoo Lee,Donghwa Kim,Han C Dan,Eric L Wu,Tatiana M Gritsko,Chuanhai Cao,Santo V Nicosia,Erica A Golemis,Wanguo Liu,Domenico Coppola,Steven S Brem,Joseph R Testa,Jin Q Cheng,

Mutations of the neurofibromatosis 2 (NF2) tumor suppressor gene have frequently been detected not only in schwannomas and other central nervous system tumors of NF2 patients but also in their sporadic counterparts and malignant tumors unrelated to the NF2 syndrome such as malignant mesothelioma, indicating a broader role for the NF2 gene in human tumorigenesis. However, the mechanisms by which the NF2 product, merlin or schwannomin, is regulated and controls cell proliferation remain elusive. Here, we identify a novel GTP-binding protein, dubbed NGB (referring to NF2-associated GTP binding protein), which binds to merlin. NGB is highly conserved between Saccharomyces cerevisiae, Caenorhabditis elegans, and human cells, and its GTP-binding region is very similar to those found in R-ras and Rap2. However, ectopic expression of NGB inhibits cell growth, cell aggregation, and tumorigenicity in tumorigenic schwanomma cells. Down-regulation and infrequent mutation of NGB were detected in human glioma cell lines and primary tumors. The interaction of NGB with merlin impairs the turnover of merlin, yet merlin does not affect the GTPase nor GTP-binding activity of NGB. Finally, the tumor suppressor functions of NGB require merlin and are linked to its ability to suppress cyclin D1 expression. Collectively, these findings indicate that NGB is a tumor suppressor that regulates and requires merlin to suppress cell proliferation.

Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein. Publishing Authors By Initials

H Lee,D Kim,HC Dan,EL Wu,TM Gritsko,C Cao,SV Nicosia,EA Golemis,W Liu,D Coppola,SS Brem,JR Testa,JQ Cheng,

For similar proteins: ubiquitins: ubiquitin research abstracts see: proteins: ubiquitins: ubiquitin research

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Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Molecular and cellular biology

VOLUME: 27

Page Numbers: 2103-19

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 0270-7306

DAY: 8

MONTH: 01

YEAR: 2007

Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8109087

Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein. Keywords Mesh Terms:

KEYWORDS: Ubiquitin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein. Information

Substance Name: GTP-Binding Proteins

Registry Number: EC 3.6.1.-

Grant and Affiliation Information for Identification and characterization of putative tumor suppressor NGB, a GTP-binding protein that interacts with the neurofibromatosis 2 protein.

AFFILIATION: Department of Pathology, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA107078-03

ACRONYM: CA

MEDLINETA: Mol Cell Biol

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