The merlin tumor suppressor interacts with Ral guanine nucleotide dissociation stimulator and inhibits its activity.
Neurofibromatosis type 2 (NF2) is the most commonly mutated gene in benign tumors of the human nervous system such as schwannomas and meningiomas. The NF2 gene encodes a protein called schwannomin or merlin, which is involved in regulating cell growth and proliferation through protein-protein interactions with various cellular proteins. In order to better understand the mechanism by which merlin exerts its function, yeast two-hybrid screening was performed and Ral guanine nucleotide dissociation stimulator (RalGDS), a downstream molecule of Ras, was identified as a merlin-binding protein. The direct interaction between merlin and RalGDS was confirmed both in vitro and in the NIH3T3 cells. The domain analyses revealed that the broad C-terminal region of merlin (aa 141-595) is necessary for the interaction with the C-terminal Ras-binding domain (RBD) of RalGDS. Functional studies showed that merlin inhibits the RalGDS-induced RalA activation, the colony formation and the cell migration in mammalian cells. These results suggest that merlin can function as a tumor suppressor by inhibiting the RalGDS-mediated oncogenic signals.
Ryu
Chung Hun
CH
Catholic Neuroscience Center, The Catholic University of Korea, Seoul 137-701, Korea.
Kim
Sae-Woong
SW
Lee
Kyu Hwa
KH
Lee
Joo Yong
JY
Kim
Hongtae
H
Lee
Woon Kyu
WK
Choi
Byung Hyune
BH
Lim
Young
Y
Kim
Young Hoon
YH
Lee
Kweon-Haeng
KH
Hwang
Tae-Kon
TK
Jun
Tae-Youn
TY
Rha
Hyoung Kyun
HK
D000818:Animals; D019556:COS Cells; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D002522:Chlorocebus aethiops; D003114:Colony-Forming Units Assay; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D041681:NIH 3T3 Cells; D025581:Neurofibromin 2 / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques; D015003:Yeasts; D020726:ral Guanine Nucleotide Exchange Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D025581:Neurofibromin 2; D020726:ral Guanine Nucleotide Exchange Factor