Reversible lysine acetylation regulates nuclear translocation of TyrRS to counteract genotoxic oxidative stress

Li, Chaoqun; Yu, Wei

doi:10.1080/23723556.2017.1293597

Cited by 3 publications

(1 citation statement)

References 11 publications

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“…TyrRSs are widely distributed in the cytoplasm under normal conditions, and they are rapidly transported into the nucleus under stress conditions (31). We determined whether the protective effect of RSV against radiation is related to the incorporation of TyrRS into the nucleus.…”

Section: Irradiation and Rsv Promote Tyrrs Nuclear Localizationmentioning

confidence: 99%

Resveratrol targets TyrRS acetylation to protect against radiation‐induced damage

Gao

et al. 2019

FASEB j.

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Resveratrol (RSV) has broad prospective applications as a radiation protection drug, but its mechanism of action is not yet clear. Here, we found that 5 µM RSV can effectively reduce the cell death caused by irradiation. Irradiation leads to G2/M phase arrest in the cell cycle, whereas RSV treatment increases S‐phase cell cycle arrest, which is associated with sirtuin 1 (SIRT1) regulation. Meanwhile, RSV promotes DNA damage repair, mainly by accelerating the efficiency of homologous recombination repair. Under oxidative stress, tyrosyl‐tRNA synthetase (TyrRS) is transported to the nucleus to protect against DNA damage. RSV can promote TyrRS acetylation, thus promoting TyrRS to enter the nucleus, where it regulates the relevant signaling proteins and reduces apoptosis and DNA damage. SIRT1 is a deacetylase, and SIRT1 knockdown or inhibition can increase TyrRS acetylation levels, further reducing radiation‐induced apoptosis after RSV treatment. Our study revealed a new radiation protection mechanism for RSV, in which the acetylation of TyrRS and its translocation into the nucleus is promoted, and this mechanism may also represent a novel protective target against irradiation.—Gao, P., Li, N., Ji, K., Wang, Y., Xu, C., Liu, Y., Wang, Q., Wang, J., He, N., Sun, Z., Du, L., Liu, Q. Resveratrol targets TyrRS acetylation to protect against radiation‐induced damage. FASEB J. 33, 8083–8093 (2019). http://www.fasebj.org

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Section: Irradiation and Rsv Promote Tyrrs Nuclear Localizationmentioning

confidence: 99%

Resveratrol targets TyrRS acetylation to protect against radiation‐induced damage

Gao

et al. 2019

FASEB j.

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Oxidative stress-CBP axis modulates MOB1 acetylation and activates the Hippo signaling pathway

Jin

Zhang

et al. 2022

Nucleic Acids Research

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Reactive oxygen species (ROS) are constantly produced in cells, an excess of which causes oxidative stress. ROS has been linked to regulation of the Hippo pathway; however, the underlying detailed mechanisms remain unclear. Here, we report that MOB1, a substrate of MST1/2 and co-activator of LATS1/2 in the canonical Hippo pathway, interacts with and is acetylated at lysine 11 by acetyltransferase CBP and deacetylated by HDAC6. MOB1-K11 acetylation stabilizes itself by reducing its binding capacity with E3 ligase Praja2 and subsequent ubiquitination. MOB1-K11 acetylation increases its phosphorylation and activates LATS1. Importantly, upstream oxidative stress signals promote MOB1 acetylation by suppressing CBP degradation, independent of MST1/2 kinase activity and HDAC6 deacetylation effect, thereby linking oxidative stress to activation of the Hippo pathway. Functionally, the acetylation-deficient mutant MOB1-K11R promotes lung cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo, compared to the wild-type MOB1. Clinically, acetylated MOB1 corresponds to better prediction of overall survival in patients with non-small cell lung cancer. Therefore, as demonstrated, an oxidative stress-CBP regulatory axis controls MOB1-K11 acetylation and activates LATS1, thereby activating the Hippo pathway and suppressing YAP/TAZ nuclear translocation and tumor progression.

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Advanced Glycosylation End Products Induced Synaptic Deficits and Cognitive Decline Through ROS-JNK-p53/miR-34c/SYT1 Axis in Diabetic Encephalopathy

Zhang

Jiang

et al. 2022

JAD

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Background: miR-34c has been found to be implicated in the pathological process of Alzheimer’s disease, diabetes, and its complications. Objective: To investigate the underlying mechanisms of miR-34c in the pathogenesis of diabetic encephalopathy (DE). Methods: Diabetes mellitus rats were developed by incorporating a high-fat diet and streptozotocin injection. Morris water maze test and novel object recognition test were used to assess the cognitive function of rats. Expression of miR-34c were detected by fluorescence in situ hybridization and qRT-PCR. Immunofluorescence and western blot were used to evaluate synaptotagmin 1 (SYT1) and AdipoR2 or other proteins. Golgi staining was performed to investigate dendritic spine density. Results: The increased miR-34c induced by advanced glycation end-products (AGEs) was mediated by ROS-JNK-p53 pathway, but not ROS-Rb-E2F1 pathway, in hippocampus of DE rats or in HT-22 cells. miR-34c negatively regulated the expression of SYT1, but not AdipoR2, in hippocampal neurons. miR-34c inhibitor rescued the AGE-induced decrease in the density of dendritic spines in primary hippocampal neurons. Administration of AM34c by the intranasal delivery increased the hippocampus levels of SYT1 and ameliorated the cognitive function in DE rats. The serum levels of miR-34c were increased in patients with DE comparing with normal controls. Conclusion: These results demonstrated that AGE-induced oxidative stress mediated increase of miR-34c through ROS-JNK-p53 pathway, resulting in synaptic deficits and cognitive decline by targeting SYT1 in DE, and the miR-34c/SYT1 axis could be considered as a novel therapeutic target for DE patients.

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Reversible lysine acetylation regulates nuclear translocation of TyrRS to counteract genotoxic oxidative stress

Cited by 3 publications

References 11 publications

Resveratrol targets TyrRS acetylation to protect against radiation‐induced damage

Resveratrol targets TyrRS acetylation to protect against radiation‐induced damage

Oxidative stress-CBP axis modulates MOB1 acetylation and activates the Hippo signaling pathway

Advanced Glycosylation End Products Induced Synaptic Deficits and Cognitive Decline Through ROS-JNK-p53/miR-34c/SYT1 Axis in Diabetic Encephalopathy

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