Dataset Information

USP45 and Spindly are part of the same complex implicated in cell migration.

ABSTRACT: Ubiquitylation is a protein modification implicated in several cellular processes. This process is reversible by the action of deubiquinating enzymes (DUBs). USP45 is a ubiquitin specific protease about which little is known, aside from roles in DNA damage repair and differentiation of the vertebrate retina. Here, by using mass spectrometry we have identified Spindly as a new target of USP45. Our data show that Spindly and USP45 are part of the same complex and that their interaction specifically depends on the catalytic activity of USP45. In addition, we describe the type of ubiquitin chains associated with the complex that can be cleaved by USP45, with a preferential activity on K48 ubiquitin chain type and potentially K6. Here, we also show that Spindly is mono-ubiquitylated and this can be specifically removed by USP45 in its active form but not by the catalytic inactive form. Lastly, we identified a new role for USP45 in cell migration, similar to that which was recently described for Spindly.

SUBMITTER: Conte C

PROVIDER: S-EPMC6158257 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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USP45 and Spindly are part of the same complex implicated in cell migration.

Conte Claudia C Griffis Eric R ER Hickson Ian I Perez-Oliva Ana B AB

Scientific reports 20180926 1

Ubiquitylation is a protein modification implicated in several cellular processes. This process is reversible by the action of deubiquinating enzymes (DUBs). USP45 is a ubiquitin specific protease about which little is known, aside from roles in DNA damage repair and differentiation of the vertebrate retina. Here, by using mass spectrometry we have identified Spindly as a new target of USP45. Our data show that Spindly and USP45 are part of the same complex and that their interaction specificall ...[more]

PMID: 30258100

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Project description:Lung adenocarcinoma (LUAD) accounts for ~40% of lung cancer cases, and the 5-year relative survival rate is no more than 1%. Dysregulation of components of striatin-interacting phosphatase and kinase (STRIPAK) complexes is associated with various diseases, including cancer. Striatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth and migration. Here, we investigated the role of STRIP2 in LUAD growth, migration and the underlying mechanisms. Analysis of data from The Cancer Genome Atlas database revealed that STRIP2 is highly expressed and predicted poor outcomes in patients with LUAD. Moreover, quantitative RT-PCR (qRT-PCR) analysis revealed that the mRNA expression of STRIP2 is greater in all tested LUAD cells than in a normal lung cell line. To investigate the function of STRIP2, we overexpressed STRIP2 in SPC-A1 cells and depleted STRIP2 in Calu-3 cells. Cell proliferation was evaluated by Cell Counting Kit-8 and colony-forming assays, and Transwell assay was employed to test cell invasion and migration. Our results indicate that STRIP2 depletion suppressed cell proliferation, invasion and migration in Calu-3 cells, and overexpression of STRIP2 had the opposite effects in SPC-A1 cells. Moreover, we discovered that STRIP2 depletion reduced the protein levels of p-Akt and phosphorylated-mammalian target of rapamycin (p-mTOR) in Calu-3 cells, whereas STRIP2 overexpression increased levels of these proteins in SPC-A1 cells. Furthermore, we found that silencing of STRIP2 clearly enhanced protein levels of E-cadherin and reduced levels of N-cadherin, Vimentin and matrix metalloproteinase-9 in Calu-3 cells, whereas overexpression of STRIP2 had the opposite effect in SPC-A1 cells. Our data indicate that STRIP2 promotes the proliferation and motility of LUAD cells, and this may be mediated through the regulation of the Akt/mTOR pathway and epithelial-mesenchymal transition. These results may facilitate the development of therapeutic strategies to treat LUAD.

Dataset Information

USP45 and Spindly are part of the same complex implicated in cell migration.

Publications

USP45 and Spindly are part of the same complex implicated in cell migration.

Similar Datasets

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