MAP, a protein interacting with a tumor suppressor, merlin, through the run domain.
Merlin (or schwannomin) is a tumor suppressor encoded by the neurofibromatosis type 2 gene. Many studies have suggested that merlin is involved in the regulation of cell growth and proliferation through interactions with various cellular proteins. To better understand the function of merlin, we tried to identify the proteins that bind to merlin using the yeast two-hybrid screening. Characterization of the positive clones revealed a protein of 749 amino acids named merlin-associated protein (MAP), which showed wide tissue distribution in Northern blot analysis. Sequence analysis revealed that MAP is a potential homologue of a yeast check-point protein, BUB2, and contains TBC, SH3, and RUN domains, thereby implicating its role in the Ras-like GTPase signal pathways. MAP and merlin were directly associated in vitro and in vivo, and colocalized in NIH3T3 cells. The RUN domain of MAP and the C-terminus of merlin appeared to be responsible for their interaction. MAP decreased the AP-1-dependent promoter activity additively with merlin in NIH3T3 cells. In addition, merlin and MAP synergistically reduced the colony formation of NIH3T3 cells. These results suggest that MAP may play a cooperative role in the merlin-mediated growth suppression of cells.
Lee
Il Kyu
IK
Department of Family Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-ku, Seoul 137-701, Republic of Korea.
Kim
Kyung-Soo
KS
Kim
Hongtae
H
Lee
Joo Yong
JY
Ryu
Chung Hun
CH
Chun
Heung Jae
HJ
Lee
Kyoung-Uk
KU
Lim
Young
Y
Kim
Young Hoon
YH
Huh
Pil-Woo
PW
Lee
Kweon-Haeng
KH
Han
Sang-Ick
SI
Jun
Tae-Youn
TY
Rha
Hyoung Kyun
HK
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D025581:Neurofibromin 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; C495141:MAP protein, mouse; D025581:Neurofibromin 2; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins