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DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells

Distant metastasis remains the leading cause of high mortality in patients with non-small-cell lung cancer (NSCLC). DIRAS3 is a candidate tumor suppressor protein that is decreased in various tumors. However, the regulatory mechanism of DIRAS3 on metastasis of NSCLC remains unclear. Here, we found t...

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Autores principales: Wang, Yingying, Wei, Minli, Su, Min, Du, Zhiyuan, Dong, Jiaxi, Zhang, Yu, Wu, Yingdi, Li, Xiaopeng, Su, Ling, Liu, Xiangguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362343/
https://www.ncbi.nlm.nih.gov/pubmed/37485351
http://dx.doi.org/10.1016/j.isci.2023.107157
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author Wang, Yingying
Wei, Minli
Su, Min
Du, Zhiyuan
Dong, Jiaxi
Zhang, Yu
Wu, Yingdi
Li, Xiaopeng
Su, Ling
Liu, Xiangguo
author_facet Wang, Yingying
Wei, Minli
Su, Min
Du, Zhiyuan
Dong, Jiaxi
Zhang, Yu
Wu, Yingdi
Li, Xiaopeng
Su, Ling
Liu, Xiangguo
author_sort Wang, Yingying
collection PubMed
description Distant metastasis remains the leading cause of high mortality in patients with non-small-cell lung cancer (NSCLC). DIRAS3 is a candidate tumor suppressor protein that is decreased in various tumors. However, the regulatory mechanism of DIRAS3 on metastasis of NSCLC remains unclear. Here, we found that DIRAS3 suppressed the migration of NSCLC cells. Besides, DIRAS3 stimulated the polyubiquitination of RAC1 and suppressed its protein expression. Furthermore, RNF19B, a member of the RBR E3 ubiquitin ligase family, was observed to be the E3 ligase involved in the DIRAS3-induced polyubiquitination of RAC1. DIRAS3 could promote the binding of RAC1 and RNF19B, thus enhancing the degradation of RAC1 by the ubiquitin-proteasome pathway. Finally, the DIRAS3-RNF19B-RAC1 axis was confirmed to be associated with the malignant progression of NSCLC. These findings may be beneficial for developing potential prognostic markers of NSCLC and may provide an effective treatment strategy.
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spelling pubmed-103623432023-07-23 DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells Wang, Yingying Wei, Minli Su, Min Du, Zhiyuan Dong, Jiaxi Zhang, Yu Wu, Yingdi Li, Xiaopeng Su, Ling Liu, Xiangguo iScience Article Distant metastasis remains the leading cause of high mortality in patients with non-small-cell lung cancer (NSCLC). DIRAS3 is a candidate tumor suppressor protein that is decreased in various tumors. However, the regulatory mechanism of DIRAS3 on metastasis of NSCLC remains unclear. Here, we found that DIRAS3 suppressed the migration of NSCLC cells. Besides, DIRAS3 stimulated the polyubiquitination of RAC1 and suppressed its protein expression. Furthermore, RNF19B, a member of the RBR E3 ubiquitin ligase family, was observed to be the E3 ligase involved in the DIRAS3-induced polyubiquitination of RAC1. DIRAS3 could promote the binding of RAC1 and RNF19B, thus enhancing the degradation of RAC1 by the ubiquitin-proteasome pathway. Finally, the DIRAS3-RNF19B-RAC1 axis was confirmed to be associated with the malignant progression of NSCLC. These findings may be beneficial for developing potential prognostic markers of NSCLC and may provide an effective treatment strategy. Elsevier 2023-06-16 /pmc/articles/PMC10362343/ /pubmed/37485351 http://dx.doi.org/10.1016/j.isci.2023.107157 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Wang, Yingying
Wei, Minli
Su, Min
Du, Zhiyuan
Dong, Jiaxi
Zhang, Yu
Wu, Yingdi
Li, Xiaopeng
Su, Ling
Liu, Xiangguo
DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells
title DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells
title_full DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells
title_fullStr DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells
title_full_unstemmed DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells
title_short DIRAS3 enhances RNF19B-mediated RAC1 ubiquitination and degradation in non-small-cell lung cancer cells
title_sort diras3 enhances rnf19b-mediated rac1 ubiquitination and degradation in non-small-cell lung cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362343/
https://www.ncbi.nlm.nih.gov/pubmed/37485351
http://dx.doi.org/10.1016/j.isci.2023.107157
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