Dataset Information

SENP5 deteriorates traumatic brain injury via SUMO2-dependent suppression of E2F1 SUMOylation.

ABSTRACT: Traumatic brain injury (TBI) represents a main public health concern during the past decade, attracting considerable interest because of its rising prevalence, wide-ranging risk factors and lifelong familial and societal influence. SUMO2 can conjugate to substrates upon various cellular stresses. Nevertheless, whether and how SUMO2-specific proteases partake in TBI is less understood. The aim of this study is to dissect the effects of SUMO-specific peptidase 5 (SENP5) on accentuating TBI in rats in an effort to unveil its underlying mechanism. SENP5 is overexpressed in hippocampal tissues of TBI rats, and inhibition of SENP5 reduces neurological function scores, decreases brain water content, inhibits apoptosis in hippocampal tissues, and attenuates brain injury caused in rats. Moreover, SENP5 inhibits the SUMOylation level of E2F transcription factor 1 (E2F1) and increases the protein expression of E2F1. Silencing of E2F1 blocks the p53 signaling pathway. Overexpression of E2F1 partially reverses the protective effect of sh-SENP5 on TBI in rats. These findings reveal an essential role of SENP5 and the SUMOylation status of E2F1 in the TBI development.

SUBMITTER: Ding Y

PROVIDER: S-EPMC10448041 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SENP5 deteriorates traumatic brain injury via SUMO2-dependent suppression of E2F1 SUMOylation.

Ding Yanfu Y Chen Feifei F Yang Weitao W Fu Xiaobin X Xie Yuanyuan Y

Acta biochimica et biophysica Sinica 20230701 8

Traumatic brain injury (TBI) represents a main public health concern during the past decade, attracting considerable interest because of its rising prevalence, wide-ranging risk factors and lifelong familial and societal influence. SUMO2 can conjugate to substrates upon various cellular stresses. Nevertheless, whether and how SUMO2-specific proteases partake in TBI is less understood. The aim of this study is to dissect the effects of SUMO-specific peptidase 5 (SENP5) on accentuating TBI in rats ...[more]

PMID: 37403456

Similar Datasets

Project description:Chemosensitivity is one of the key factors affecting the therapeutic effect on cancer, but the clinical application of corresponding drugs is rare. Hypoxia, a common feature of many solid tumors, including hepatocellular carcinoma (HCC), has been associated with resistance to chemotherapy in part through the activation of the Sonic Hedgehog (SHh) pathway. Hypoxia has also been associated with the increased SUMOylation of multiple proteins, including GLI family proteins, which are key mediators of SHh signaling, and has become a promising target to develop drug-resistant drugs for cancer treatment. However, there are few target drugs to abrogate chemotherapy resistance. Saikosaponin-d (Ssd), one of the main bioactive components of Radix bupleuri, has been reported to exert multiple biological effects, including anticancer activity. Here, we first found that Ssd inhibits the malignant phenotype of HCC cells while increasing their sensitivity to the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) drug system under hypoxia in vitro and in vivo. Furthermore, we had explored that GLI family activation and extensive protein SUMOylation were characteristics of HCC cells, and hypoxia could activate the SHh pathway and promote epithelial-mesenchymal transition (EMT), invasion, and chemosensitivity in HCC cells. SUMOylation is required for hypoxia-dependent activation of GLI proteins. Finally, we found that Ssd could reverse the effects promoted by hypoxia, specifically active sentrin/small ubiquitin-like modifier (SUMO)-specific protease 5 (SENP5), a SUMO-specific protease, in a time- and dose-dependent manner while inhibiting the expression of SUMO1 and GLI proteins. Together, these findings confirm the important role of Ssd in the chemoresistance of liver cancer, provide some data support for further understanding the molecular mechanisms of Ssd inhibition of malignant transformation of HCC cells, and provide a new perspective for the application of traditional Chinese medicine in the chemical resistance of liver cancer.

Dataset Information

SENP5 deteriorates traumatic brain injury via SUMO2-dependent suppression of E2F1 SUMOylation.

Publications

SENP5 deteriorates traumatic brain injury via SUMO2-dependent suppression of E2F1 SUMOylation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets