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TRIM69 inhibits cataractogenesis by negatively regulating p53
Ultraviolet B (UVB) irradiation can induce reactive oxygen species (ROS) production and apoptosis in human lens epithelial cells (HLECs), thus leading to the formation of cataracts. We studied the role of tripartite motif 69 (TRIM69) in cataract formation. The expression of TRIM69 protein was down-r...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402377/ https://www.ncbi.nlm.nih.gov/pubmed/30844644 http://dx.doi.org/10.1016/j.redox.2019.101157 |
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author | Rong, Xianfang Rao, Jun Li, Dan Jing, Qinghe Lu, Yi Ji, Yinghong |
author_facet | Rong, Xianfang Rao, Jun Li, Dan Jing, Qinghe Lu, Yi Ji, Yinghong |
author_sort | Rong, Xianfang |
collection | PubMed |
description | Ultraviolet B (UVB) irradiation can induce reactive oxygen species (ROS) production and apoptosis in human lens epithelial cells (HLECs), thus leading to the formation of cataracts. We studied the role of tripartite motif 69 (TRIM69) in cataract formation. The expression of TRIM69 protein was down-regulated in both human cataract capsule tissues and HLECs treated with UVB, whereas the expression of p53 protein exhibited an opposite trend. Ectopic expression of TRIM69 in HLECs significantly suppressed UVB-induced apoptosis and ROS production, whereas knockdown of TRIM69 promoted apoptosis and ROS production. TRIM69 can interact with p53 and induce its ubiquitination. The effects of TRIM69 overexpression in UVB-induced cell apoptosis and ROS production was clearly weakened by p53 overexpression, thus suggesting a role for p53 in TRIM69 functions. Furthermore, inhibition of ROS mitigated the effects of UVB irradiation on ROS production, cell apoptosis, forkhead box protein 3a (Foxo3a) phosphorylation, and TRIM69 expression. Additionally, Foxo3a overexpression significantly enhanced TRIM69 promoter activity, whereas Foxo3a knockdown had the opposite effect. In conclusion, we provide the first demonstration that Foxo3a is a potential transcription factor for TRIM69, and TRIM69 induces p53 ubiquitination. These results suggest that the Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation. |
format | Online Article Text |
id | pubmed-6402377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-64023772019-03-18 TRIM69 inhibits cataractogenesis by negatively regulating p53 Rong, Xianfang Rao, Jun Li, Dan Jing, Qinghe Lu, Yi Ji, Yinghong Redox Biol Research Paper Ultraviolet B (UVB) irradiation can induce reactive oxygen species (ROS) production and apoptosis in human lens epithelial cells (HLECs), thus leading to the formation of cataracts. We studied the role of tripartite motif 69 (TRIM69) in cataract formation. The expression of TRIM69 protein was down-regulated in both human cataract capsule tissues and HLECs treated with UVB, whereas the expression of p53 protein exhibited an opposite trend. Ectopic expression of TRIM69 in HLECs significantly suppressed UVB-induced apoptosis and ROS production, whereas knockdown of TRIM69 promoted apoptosis and ROS production. TRIM69 can interact with p53 and induce its ubiquitination. The effects of TRIM69 overexpression in UVB-induced cell apoptosis and ROS production was clearly weakened by p53 overexpression, thus suggesting a role for p53 in TRIM69 functions. Furthermore, inhibition of ROS mitigated the effects of UVB irradiation on ROS production, cell apoptosis, forkhead box protein 3a (Foxo3a) phosphorylation, and TRIM69 expression. Additionally, Foxo3a overexpression significantly enhanced TRIM69 promoter activity, whereas Foxo3a knockdown had the opposite effect. In conclusion, we provide the first demonstration that Foxo3a is a potential transcription factor for TRIM69, and TRIM69 induces p53 ubiquitination. These results suggest that the Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation. Elsevier 2019-03-02 /pmc/articles/PMC6402377/ /pubmed/30844644 http://dx.doi.org/10.1016/j.redox.2019.101157 Text en © 2019 The Authors http://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 | Research Paper Rong, Xianfang Rao, Jun Li, Dan Jing, Qinghe Lu, Yi Ji, Yinghong TRIM69 inhibits cataractogenesis by negatively regulating p53 |
title | TRIM69 inhibits cataractogenesis by negatively regulating p53 |
title_full | TRIM69 inhibits cataractogenesis by negatively regulating p53 |
title_fullStr | TRIM69 inhibits cataractogenesis by negatively regulating p53 |
title_full_unstemmed | TRIM69 inhibits cataractogenesis by negatively regulating p53 |
title_short | TRIM69 inhibits cataractogenesis by negatively regulating p53 |
title_sort | trim69 inhibits cataractogenesis by negatively regulating p53 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402377/ https://www.ncbi.nlm.nih.gov/pubmed/30844644 http://dx.doi.org/10.1016/j.redox.2019.101157 |
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