دورية أكاديمية
RhoBTB1 interacts with ROCKs and inhibits invasion.
| العنوان: | RhoBTB1 interacts with ROCKs and inhibits invasion. |
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| المؤلفون: | Haga RB; Randall Centre of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, U.K., Garg R; Randall Centre of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, U.K., Collu F; Randall Centre of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, U.K., Borda D'Agua B; Randall Centre of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, U.K., Menéndez ST; Randall Centre of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, U.K., Colomba A; Randall Centre of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, U.K., Fraternali F; Randall Centre of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, U.K., Ridley AJ; Randall Centre of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, U.K. anne.ridley@bristol.ac.uk.; School of Cellular and Molecular Medicine, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, U.K. |
| المصدر: | The Biochemical journal [Biochem J] 2019 Sep 13; Vol. 476 (17), pp. 2499-2514. Date of Electronic Publication: 2019 Sep 13. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Published by Portland Press on behalf of the Biochemical Society Country of Publication: England NLM ID: 2984726R Publication Model: Electronic Cited Medium: Internet ISSN: 1470-8728 (Electronic) Linking ISSN: 02646021 NLM ISO Abbreviation: Biochem J Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society |
| مواضيع طبية MeSH: | Neoplasm Proteins/*metabolism , Prostatic Neoplasms/*metabolism , rho GTP-Binding Proteins/*metabolism , rho-Associated Kinases/*metabolism, Animals ; COS Cells ; Chlorocebus aethiops ; Cullin Proteins/genetics ; Cullin Proteins/metabolism ; HeLa Cells ; Humans ; Male ; Neoplasm Invasiveness ; Neoplasm Proteins/genetics ; PC-3 Cells ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; rho GTP-Binding Proteins/genetics ; rho-Associated Kinases/genetics |
| مستخلص: | RhoBTB1 is an atypical Rho GTPase with two BTB domains in addition to its Rho domain. Although most Rho GTPases regulate actin cytoskeletal dynamics, RhoBTB1 is not known to affect cell shape or motility. We report that RhoBTB1 depletion increases prostate cancer cell invasion and induces elongation in Matrigel, a phenotype similar to that induced by depletion of ROCK1 and ROCK2. We demonstrate that RhoBTB1 associates with ROCK1 and ROCK2 and its association with ROCK1 is via its Rho domain. The Rho domain binds to the coiled-coil region of ROCK1 close to its kinase domain. We identify two amino acids within the Rho domain that alter RhoBTB1 association with ROCK1. RhoBTB1 is a substrate for ROCK1, and mutation of putative phosphorylation sites reduces its association with Cullin3, a scaffold for ubiquitin ligases. We propose that RhoBTB1 suppresses cancer cell invasion through interacting with ROCKs, which in turn regulate its association with Cullin3. Via Cullin3, RhoBTB1 has the potential to affect protein degradation. (© 2019 The Author(s).) |
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| معلومات مُعتمدة: | 15961 United Kingdom CRUK_ Cancer Research UK; United Kingdom MRC_ Medical Research Council; C6620/A15961 United Kingdom CRUK_ Cancer Research UK; United Kingdom BB_ Biotechnology and Biological Sciences Research Council |
| فهرسة مساهمة: | Keywords: Cullin3; Rho GTPases; Rho-kinases; RhoBTB; cell invasion; phosphorylation |
| المشرفين على المادة: | 0 (CUL3 protein, human) 0 (Cullin Proteins) 0 (Neoplasm Proteins) 0 (RhoBTB1 protein, human) EC 2.7.11.1 (ROCK1 protein, human) EC 2.7.11.1 (ROCK2 protein, human) EC 2.7.11.1 (rho-Associated Kinases) EC 3.6.5.2 (rho GTP-Binding Proteins) |
| تواريخ الأحداث: | Date Created: 20190822 Date Completed: 20200318 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| مُعرف محوري في PubMed: | PMC6744581 |
| DOI: | 10.1042/BCJ20190203 |
| PMID: | 31431478 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1470-8728 |
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| DOI: | 10.1042/BCJ20190203 |