Dataset Information

SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.

ABSTRACT: Deleted in breast cancer 1 (DBC1) was initially identified from a homozygously deleted region in human chromosome 8p21. It has been well established that DBC1 plays a dual role during cancer development. Depending on the physiological context, it can promote or inhibit tumorigenesis. Whether it plays a role in lens pathogenesis remains elusive. In the present study, we demonstrated that DBC1 is highly expressed in lens epithelial cells from different vertebrates and in retina pigment epithelial cells as well. Moreover, DBC1 is SUMOylated through SUMO1 conjugation at K591 residue in human and mouse lens epithelial cells. The SUMOylated DBC1 is localized in the nucleus and plays an essential role in promoting stress-induced apoptosis. Silence of DBC1 attenuates oxidative stress-induced apoptosis. In contrast, overexpression of DBC1 enhances oxidative stress-induced apoptosis, and this process depends on p53. Mechanistically, DBC1 interacts with p53 to regulate its phosphorylation status at multiple sites and the SUMOylation of DBC1 enhances its interaction with p53. Together, our results identify that DBC1 is an important regulator mediating stress-induced apoptosis in lens, and thus participates in control of lens cataractogenesis.

SUBMITTER: Wang Y

PROVIDER: S-EPMC10522365 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.

Wang Yan Y Wang Jing-Miao JM Xiao Yuan Y Hu Xue-Bin XB Zheng Shu-Yu SY Fu Jia-Ling JL Zhang Lan L Gan Yu-Wen YW Liang Xing-Miao XM Li David Wan-Cheng DW

Aging 20230907 17

Deleted in breast cancer 1 (DBC1) was initially identified from a homozygously deleted region in human chromosome 8p21. It has been well established that DBC1 plays a dual role during cancer development. Depending on the physiological context, it can promote or inhibit tumorigenesis. Whether it plays a role in lens pathogenesis remains elusive. In the present study, we demonstrated that DBC1 is highly expressed in lens epithelial cells from different vertebrates and in retina pigment epithelial ...[more]

PMID: 37683133

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Project description:Evidence is emerging for apoptosis gene expression in the lens during development. Therefore, here we used a filter array to assess expression of 243 apoptosis-related genes in the developing postnatal mouse lens using (33)P labelled cDNA synthesized from p7 and p14 mouse lenses. We demonstrated that 161 apoptosis-related genes were expressed at levels significantly above background and 20 genes were potentially significantly differentially expressed (P<0.05) by at least 2-fold between p7 and p14. We used RT-PCR to confirm expression of these genes in newborn, p7, p14 and 4 wk mouse lens cDNA samples. Expression of 19/20 of the genes examined was confirmed, while 5 genes (Huntingtin, Mdm2, Dffa, galectin-3 and Mcl-1) were confirmed as differentially regulated between p7 and p14. RT-PCR was also used to examine the expression of the chick homologues of the most-highly expressed and/or potentially differentially regulated genes in chick embryo lenses at E6-E16. The majority of genes expressed in the postnatal mouse lens were also expressed in the chick embryo lens. Western blotting confirmed developmentally regulated expression of Axl and Mcl-1 during mouse lens development and of Mdm2, Mdm4/X and p53 during mouse and chick lens development. Western blotting also revealed the presence of p53 and Mdm4/X splice variants and/or proteolytic cleavage products in the developing lens. Since Mdm2 is a regulator of the tumour suppressor gene p53, we chose to thoroughly investigate the spatio-temporal expression patterns of p53, Mdm2 and the functionally related Mdm4/X in mouse lens development at E12.5-E16.5 using immunocytochemistry. We also examined Mdm2 expression patterns during chick lens development at E6-E16 and Mdm4/X and p53 at E14. Expression of Mdm2, Mdm4/X and p53 was spatio-temporally regulated in various compartments of the developing lens in both mouse and chick, including lens epithelial and lens fibre cells, indicating potential roles for these factors in regulation of lens epithelial cell proliferation and/or lens fibre cell differentiation This study provides a thorough initial analysis of apoptosis gene expression in the postnatal mouse lens and provides a resource for further investigation of the roles in lens development of the apoptosis genes identified. Furthermore, building on the array studies, we present the first spatio-temporal analysis of expression of p53 pathway molecules (p53, Mdm2 and Mdm4/X) in both developing mouse and chick lenses, suggesting a potential role for the p53/Mdm2 pathway in lens development, which merits further functional analysis.

Dataset Information

SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.

Publications

SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.

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