Exploring the Role and Mechanism of pAMPK<i>α</i>‐Mediated Dysregulation of Brf1 and RNA Pol III Genes

Wu, Teng; Zhang, Dongkun; Lin, Mingen; Yu, Lei; Dai, Ting; Li, Shuai; Yu, Feng-Hai; Lü, Lei; Zheng, Liling; Zhong, Shuming

doi:10.1155/2021/5554932

Cited by 5 publications

(1 citation statement)

References 43 publications

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“…We performed immunoblotting analysis according to standard procedures as previously described. 42 The antibodies used in our study were against the following proteins: NADK1 (Proteintech, 15548-1-AP, 1: 1000), GPER1 (Abcam, ab39742, 1: 1000), NADK2 (Proteintech, 26352-1-AP, 1: 1000), p-PKC (Abcam, ab109539, 1: 1000), PKC (Abcam, ab181558, 1: 1000), PKC substrate (CST, 6967, 1: 1000), p-AKT (Ser473) (CST, 4060S, 1: 1000), AKT (CST, 9272S, 1: 1000), G6PD (Proteintech, 25 413-1-AP, 1: 1000), NNT (Proteintech, 13442-2-AP, 1: 1000) and GAPDH (Proteintech, 10494-1-AP, 1: 3000). For ubiquitination assays, GC cells were treated with the protein synthesis inhibitor cycloheximide (CHX) (AbMole, Cat No.…”

Section: Immunoblot Analysis Immunofluorescence and Immunoprecipitationmentioning

confidence: 99%

G‐protein‐coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1‐mediated redox modulation

Wu,

Ding,

Wang

et al. 2024

The FASEB Journal

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Adipose tissue is the second most important site of estrogen production, where androgens are converted into estrogen by aromatase. While gastric cancer patients often develop adipocyte‐rich peritoneal metastasis, the underlying mechanism remains unclear. In this study, we identified the G‐protein‐coupled estrogen receptor (GPER1) as a promoter of gastric cancer peritoneal metastasis. Functional in vitro studies revealed that β‐Estradiol (E2) or the GPER1 agonist G1 inhibited anoikis in gastric cancer cells. Additionally, genetic overexpression or knockout of GPER1 significantly inhibited or enhanced gastric cancer cell anoikis in vitro and peritoneal metastasis in vivo, respectively. Mechanically, GPER1 knockout disrupted the NADPH pool and increased reactive oxygen species (ROS) generation. Conversely, overexpression of GPER1 had the opposite effects. GPER1 suppressed nicotinamide adenine dinucleotide kinase 1(NADK1) ubiquitination and promoted its phosphorylation, which were responsible for the elevated expression of NADK1 at protein levels and activity, respectively. Moreover, genetic inhibition of NADK1 disrupted NADPH and redox homeostasis, leading to high levels of ROS and significant anoikis, which inhibited lung and peritoneal metastasis in cell‐based xenograft models. In summary, our study suggests that inhibiting GPER1‐mediated NADK1 activity and its ubiquitination may be a promising therapeutic strategy for peritoneal metastasis of gastric cancer.

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Section: Immunoblot Analysis Immunofluorescence and Immunoprecipitationmentioning

confidence: 99%

G‐protein‐coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1‐mediated redox modulation

Wu,

Ding,

Wang

et al. 2024

The FASEB Journal

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Maf1 Cooperates with Progesterone Receptor to Repress RNA Polymerase III Transcription of Select tRNAs

Finlay-Schultz,

Paul,

Erickson

et al. 2024

Preprint

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Progesterone receptors (PR) can regulate transcription by RNA Polymerase III (Pol III), which transcribes small non-coding RNAs, including all transfer RNAs (tRNAs). We have previously demonstrated that PR is associated with the Pol III complex at tRNA genes and that progestins downregulate tRNA transcripts in breast tumor models. To further elucidate the mechanism of PR-mediated regulation of Pol III, we studied the interplay between PR, the Pol III repressor Maf1, and TFIIIB, a core transcription component. ChIP-seq was performed for PR, the Pol III subunit POLR3A, the TFIIIB component Brf1, and Maf1 in breast cancer cells with or without progestin treatment. Upon progestin exposure, PR localized to approximately half of POLR3A-occupied tRNA genes, with Maf1 co-recruited to many of these PR-POLR3A sites. While progestin treatment did not significantly alter the number of tRNA genes occupied by Pol III or Brf1, Brf1 occupancy was stabilized, as indicated by increased peak amplitudes. Analysis of nascent tRNA transcription revealed a specific progestin-induced downregulation of approximately one-third of highly expressed tRNA genes. This repression was significantly reduced by Maf1 knockdown, indicating that Maf1 is necessary for PR-mediated tRNA transcription downregulation. Overall, these findings demonstrate a ligand-dependent PR-mediated repression of tRNA transcription through Maf1.

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[Retracted] ROS Signaling‐Mediated Novel Biological Targets: Brf1 and RNA Pol III Genes

Zheng

Lin

Zhong

2021

Oxidative Medicine and Cellular Longevity

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Biomolecule metabolism produces ROS (reactive oxygen species) under physiological and pathophysiological conditions. Dietary factors (alcohol) and carcinogens (EGF, DEN, and MNNG) also induce the release of ROS. ROS often causes cell stress and tissue injury, eventually resulting in disorders or diseases of the body through different signaling pathways. Normal metabolism of protein is critically important to maintain cellular function and body health. Brf1 (transcript factor II B-related factor 1) and its target genes, RNA Pol III genes (RNA polymerase III-dependent genes), control the process of protein synthesis. Studies have demonstrated that the deregulation of Brf1 and its target genes is tightly linked to cell proliferation, cell transformation, tumor development, and human cancers, while alcohol, EGF, DEN, and MNNG are able to induce the deregulation of these genes through different signaling pathways. Therefore, it is very important to emphasize the roles of these signaling events mediating the processes of Brf1 and RNA Pol III gene transcription. In the present paper, we mainly summarize our studies on signaling events which mediate the deregulation of these genes in the past dozen years. These studies indicate that Brf1 and RNA Pol III genes are novel biological targets of ROS.

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Exploring the Role and Mechanism of pAMPKα‐Mediated Dysregulation of Brf1 and RNA Pol III Genes

Cited by 5 publications

References 43 publications

G‐protein‐coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1‐mediated redox modulation

G‐protein‐coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1‐mediated redox modulation

Maf1 Cooperates with Progesterone Receptor to Repress RNA Polymerase III Transcription of Select tRNAs

[Retracted] ROS Signaling‐Mediated Novel Biological Targets: Brf1 and RNA Pol III Genes

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