Accumulating evidence suggests that developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved GTP-binding protein, plays an important role in regulating cell growth, inflammation, and mitochondria dynamics. However, the effect of DRG2 in aging remains unclear. In this study, we found that endogenous DRG2 protein expression is upregulated in oxidative stress-induced premature senescence models and tissues of aged mice. Ectopic expression of DRG2 significantly promoted senescence-associated -galactosidase (SA--gal) activity and inhibited cell growth, concomitant with increase in levels of acetyl (ac)-p53 (Lys382), ac-nuclear factor-kB (NF-B) p65 (Lys310), p21 , and p16 and a decrease in cyclin D1. In this process, reactive oxygen species (ROS) and phosphorylation of H2A histone family member X (H2A.X), forming -H2A.X, were enhanced. Mechanistically, ectopic expression of DRG2 downregulated Sirtuin-1 (SIRT1), resulting in augmented acetylation of p53 and NF-B p65. Additionally, DRG2 knockdown significantly abolished oxidative stress-induced premature senescence. Our results provide a possible molecular mechanism for investigation of cellular senescence and aging regulated by DRG2.
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http://dx.doi.org/10.1155/2021/7301373 | DOI Listing |
BMC Genomics
October 2024
State Key Laboratory of Mariculture Breeding, College of Ocean and Earth Sciences, Xiamen University, Xiamen, 361102, China.
Structure
November 2024
Institute of Cancer and Genomics Sciences, University of Birmingham, B15 2TT Birmingham, UK. Electronic address:
Eukaryotes have two paralogous developmentally regulated GTP-binding (DRG) proteins: DRG1 and DRG2, both of which have a conserved binding partner called DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively. DFRPs are important for the function of DRGs and interact with their respective DRG via a conserved region called the DFRP domain. Despite being highly similar, DRG1 and DRG2 have strict binding specificity for their respective DFRP.
View Article and Find Full Text PDFCell Death Discov
May 2024
Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells.
View Article and Find Full Text PDFClin Immunol
December 2023
Department of Biological Sciences, University of Ulsan, Ulsan 44610, Republic of Korea; Basic-Clinical Convergence Research Institute, University of Ulsan, Ulsan 44610, Republic of Korea. Electronic address:
Innate immune response is critical for the control of Listeria monocytogenes infection. Here, we identified developmentally regulated GTP-binding protein 2 (DRG2) in macrophages as a major regulator of the innate immune response against L. monocytogenes infection.
View Article and Find Full Text PDFFront Immunol
September 2022
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Accumulating evidence has demonstrated that the immune cells have an emerging role in controlling anti-tumor immune responses and tumor progression. The comprehensive role of mast cell in glioma has not been illustrated yet. In this study, 1,991 diffuse glioma samples were collected from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA).
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