title: Ubiquitin-specific protease 11 functions as a tumor suppressor by modulating Mgl-1 protein to regulate cancer cell growth.
abstract: The Lethal giant larvae (Lgl) gene encodes a cortical cytoskeleton protein, Lgl, and is involved in maintaining cell polarity and epithelial integrity. Previously, we observed that Mgl-1, a mammalian homologue of the Drosophila tumor suppressor protein Lgl, is subjected to degradation via ubiquitin-proteasome pathway, and scaffolding protein RanBPM prevents the turnover of the Mgl-1 protein. Consequently, overexpression of RanBPM enhances Mgl-1-mediated cell proliferation and migration. Here, we analyzed the ability of ubiquitin-specific protease 11 (USP11) as a novel regulator of Mgl-1 and it requires RanBPM to regulate proteasomal degradation of Mgl-1. USP11 showed deubiquitinating activity and stabilized Mgl-1 protein. However, USP11-mediated Mgl-1 stabilization was inhibited in RanBPM-knockdown cells. Furthermore, in the cancer cell migration, the regulation of Mgl-1 by USP11 required RanBPM expression. In addition, an in vivo study revealed that depletion of USP11 leads to tumor formation. Taken together, the results indicated that USP11 functions as a tumor suppressor through the regulation of Mgl-1 protein degradation via RanBPM.
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Key-Hwan
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Bharathi
authors.initials: B
authors.lastname: Suresh
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Suresh
authors.initials: S
authors.lastname: Ramakrishna
authors.affiliation: Department of Biomedical Science, CHA University, Gyeonggi-Do 463-400, Republic of Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Baek
mesh_terms: D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D037181:Lectins, C-Type / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D037181:Lectins, C-Type; C506225:MGL lectin, human; D009687:Nuclear Proteins; C116005:Ran binding protein 9; C101359:USP11 protein, human; D013869:Thiolester Hydrolases
keywords: RanBPM; UAF1; USP11; deubiquitinating enzyme; ubiquitin