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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...

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Autores principales: Rong, Xianfang, Rao, Jun, Li, Dan, Jing, Qinghe, Lu, Yi, Ji, Yinghong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
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.
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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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