Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging
Abstract Background Ultraviolet A (UVA) irradiation can lead to skin damage and premature skin aging known as photoaging. This work found that UVA irradiation caused an imbalance between dermal matrix synthesis and degradation through the aberrant upregulation of transgelin (TAGLN) and studied the u...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-023-01029-z |
| _version_ | 1827952522238623744 |
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| author | Yinan Li Xiu Huang Jing Jin Haohao Zhang Kai Yang Jingxia Han Ying Lv Yu Sun Cheng Yao Tingting Lin Caibin Zhu Huijuan Liu |
| author_facet | Yinan Li Xiu Huang Jing Jin Haohao Zhang Kai Yang Jingxia Han Ying Lv Yu Sun Cheng Yao Tingting Lin Caibin Zhu Huijuan Liu |
| author_sort | Yinan Li |
| collection | DOAJ |
| description | Abstract Background Ultraviolet A (UVA) irradiation can lead to skin damage and premature skin aging known as photoaging. This work found that UVA irradiation caused an imbalance between dermal matrix synthesis and degradation through the aberrant upregulation of transgelin (TAGLN) and studied the underlying molecular mechanism. Results Co-immunoprecipitation and proximal ligation assay results showed that TAGLN can interact with USP1. USP1 can be retained in the cytoplasm by TAGLN in UVA-induced cells, which inhibits the interaction between USP1/zinc finger E-box binding homeobox 1 (ZEB1), promote the ubiquitination degradation of ZEB1, and lead to photoaging. TAGLN knockdown can release USP1 retention and help human skin fibroblasts (HSFs) resist UVA-induced damage. The interactive interface inhibitors of TAGLN/USP1 were screened via virtual docking to search for small molecules that inhibit photoaging. Zerumbone (Zer), a natural product isolated from Zingiber zerumbet (L.) Smith, was screened out. Zer can competitively bind TAGLN to reduce the retention of USP1 in the cytoplasm and the degradation of ZEB1 ubiquitination in UV-induced HSFs. The poor solubility and permeability of Zer can be improved by preparing it as a nanoemulsion, which can effectively prevent skin photoaging caused by UVA in wild-type (WT) mice. Zer cannot effectively resist the photoaging caused by UVA in Tagln −/− mice because of target loss. Conclusions The present results showed that the interaction of TAGLN and USP1 can promote ZEB1 ubiquitination degradation in UV-induced skin photoaging, and Zer can be used as an interactive interface inhibitor of TAGLN/USP1 to prevent photoaging. |
| first_indexed | 2024-04-09T13:58:55Z |
| format | Article |
| id | doaj.art-715e15de17d14438ae3c6b7f7b54d56b |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-09T13:58:55Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-715e15de17d14438ae3c6b7f7b54d56b2023-05-07T11:25:21ZengBMCCell & Bioscience2045-37012023-05-0113111410.1186/s13578-023-01029-zInteraction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoagingYinan Li0Xiu Huang1Jing Jin2Haohao Zhang3Kai Yang4Jingxia Han5Ying Lv6Yu Sun7Cheng Yao8Tingting Lin9Caibin Zhu10Huijuan Liu11Cheermore Cosmetic Dermatology LaboratoryCheermore Cosmetic Dermatology LaboratoryCheermore Cosmetic Dermatology LaboratoryCheermore Cosmetic Dermatology LaboratoryCheermore Cosmetic Dermatology LaboratoryCheermore Cosmetic Dermatology LaboratoryState Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai UniversityCheermore Cosmetic Dermatology LaboratoryMedical plastic and cosmetic center, Tianjin Branch of National Clinical Research Center for Ocular Disease, Tianjin Medical University Eye HospitalCheermore Cosmetic Dermatology LaboratoryCheermore Cosmetic Dermatology LaboratoryAbstract Background Ultraviolet A (UVA) irradiation can lead to skin damage and premature skin aging known as photoaging. This work found that UVA irradiation caused an imbalance between dermal matrix synthesis and degradation through the aberrant upregulation of transgelin (TAGLN) and studied the underlying molecular mechanism. Results Co-immunoprecipitation and proximal ligation assay results showed that TAGLN can interact with USP1. USP1 can be retained in the cytoplasm by TAGLN in UVA-induced cells, which inhibits the interaction between USP1/zinc finger E-box binding homeobox 1 (ZEB1), promote the ubiquitination degradation of ZEB1, and lead to photoaging. TAGLN knockdown can release USP1 retention and help human skin fibroblasts (HSFs) resist UVA-induced damage. The interactive interface inhibitors of TAGLN/USP1 were screened via virtual docking to search for small molecules that inhibit photoaging. Zerumbone (Zer), a natural product isolated from Zingiber zerumbet (L.) Smith, was screened out. Zer can competitively bind TAGLN to reduce the retention of USP1 in the cytoplasm and the degradation of ZEB1 ubiquitination in UV-induced HSFs. The poor solubility and permeability of Zer can be improved by preparing it as a nanoemulsion, which can effectively prevent skin photoaging caused by UVA in wild-type (WT) mice. Zer cannot effectively resist the photoaging caused by UVA in Tagln −/− mice because of target loss. Conclusions The present results showed that the interaction of TAGLN and USP1 can promote ZEB1 ubiquitination degradation in UV-induced skin photoaging, and Zer can be used as an interactive interface inhibitor of TAGLN/USP1 to prevent photoaging.https://doi.org/10.1186/s13578-023-01029-zTAGLNZerumboneZEB1PhotoagingDeubiquitination |
| spellingShingle | Yinan Li Xiu Huang Jing Jin Haohao Zhang Kai Yang Jingxia Han Ying Lv Yu Sun Cheng Yao Tingting Lin Caibin Zhu Huijuan Liu Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging Cell & Bioscience TAGLN Zerumbone ZEB1 Photoaging Deubiquitination |
| title | Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging |
| title_full | Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging |
| title_fullStr | Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging |
| title_full_unstemmed | Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging |
| title_short | Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging |
| title_sort | interaction of tagln and usp1 promotes zeb1 ubiquitination degradation in uv induced skin photoaging |
| topic | TAGLN Zerumbone ZEB1 Photoaging Deubiquitination |
| url | https://doi.org/10.1186/s13578-023-01029-z |
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