The Mitochondrial Protein MAVS Stabilizes p53 to Suppress Tumorigenesis

Zhang, Wanchuan; Gong, Jing; Yang, Huan; Wan, Luming; Peng, Yumeng; Wang, Xiaolin; Sun, Jin Peng; Li, Feng; Geng, Yunqi; Li, Dongyu; Liu, Ning; Mei, Gangwu; Cao, Yuan; Yan, Qiulin; Li, Huilong; Zhang, Yanhong; He, Xiaoqing; Zhang, Qiaozhi; Zhang, Rui; Wu, Feixiang; Zhong, Hui; Wei, Congwen

doi:10.1016/j.celrep.2019.12.051

Cited by 23 publications

(20 citation statements)

References 43 publications

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“…K48-linked polyubiquitination of p53 can be regulated by various molecules. For instance, MAVS and ATF3 can stabilize p53 by preventing p53 from MDM2-mediated ubiquitination [ 186 , 187 ]. ACP5 mediated p53 phosphorylation enhanced the ubiquitination and degradation of p53 [ 188 ].…”

Section: Ubiquitination and Transcription Factorsmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

221

178

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Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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Section: Ubiquitination and Transcription Factorsmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

221

178

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“…Additionally, the direct influence of mitochondrial targeted MITF as a protein interactor in context to its phosphorylation state at Serine 73 was presented in this work. Even though nuclear transcription factors are best known for their major role in gene expression, recent studies on different other transcription factors like p53 [25], CREB [26] and STAT3 [27,28] translocation to mitochondria denotes their other functionality as a direct protein interactor to influence mitochondrial bioenergetics. During immunological activation of mast cells, MITF-Serine 73 phosphorylation was noted and overexpression of the phosphorylated mimicking mitochondrial MITF-S73D caused elevated degranulation compared to control cells.…”

Section: Discussionmentioning

confidence: 99%

The Critical Role Played by Mitochondrial MITF Serine 73 Phosphorylation in Immunologically Activated Mast Cells

Paruchuru

Sharmila

Razin

2022

Cells

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In recent years, growing evidence has indicated the pivotal role of mitochondria in mast cell immunological activation. We have previously reported a decrease in degranulation and cytokine secretion following the inhibition of pyruvate dehydrogenase (PDH) either by CPI-613 (PDH inhibitor/anti-cancer drug) or through its interaction with mitochondrial microphthalmia-associated transcription factor (MITF). In the present study, we further explored the role played by mitochondrial MITF in mast cell exocytosis using rat basophil leukemia cells [RBL], as well as mouse bone marrow-derived mast cells (BMMCs). Here, we report that mast cell degranulation, cytokine secretion and oxidative phosphorylation (OXPHOS) activities were associated with phosphorylation of Serine 73 of mitochondrial MITF, controlled by extracellular signals regulated by protein kinase (ERK1/2) activity. Also, we report here that decreased OXPHOS activity following ERK1/2 inhibition (U0126 treatment) during IgE-Ag activation was mediated by the dephosphorylation of Serine 73 mitochondrial MITF, which inhibited its association with PDH. This led to a reduction in mast cell reactivity. In addition, a phosphorylation-mimicking mitochondrial MITF-S73D positively regulated the mitochondrial activity, thereby supporting mast cell degranulation. Thus, the present research findings highlight the prominence of mitochondrial MITF Serine 73 phosphorylation in immunologically activated mast cells.

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“…The mitochondrial antiviral signaling (MAVS) protein acts as an essential adaptor in the RIG-I-like receptor (RLR) signaling pathway, which plays an important role in host defenses against viral infections by inducing IFN-I production [19]. MAVS low expression was associated with a wide spectrum of malignant tumors [20]. Hence, MAVS activation may have tumor-suppressive effects in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Model Based On Cytosolic DNA Sensing-Related Gene Signature for Pancreatic Cancer

Xu¹,

Yang²,

Zhao³

et al. 2021

Preprint

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Objective: Pancreatic cancer (PC) is one of the most malignant tumors. Cytosolic DNA sensing have been found to play an essential role in tumor. In this study, a cytosolic DNA sensing-related genes (CDSRGs) signature was constructed and the potential mechanisms also been discussed.Methods: The RNA expression and clinical data of PC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Subsequently, univariate (UCR) and multivariate Cox regression (MCR) analyses were conducted to establish a prognostic model in the TCGA patients, which was verified by GEO patients. Cancer immune infiltrates were investigated via single sample gene set enrichment analysis (ssGSEA) and Tumor Immune Estimation Resource (TIMER). Finally, Gene Set Enrichment Analysis (GSEA) was used to investigate the related signaling pathways.Results: A prognostic model comprising four genes (POLR2E,IL18, MAVS, and FADD) was established. The survival rate of patients in the low-risk group was significantly higher than that of patients in the high-risk group. In addition, CDSRGs-risk score was proved as an independent prognostic factor in PC. Immune infiltrates and drug sensitivity are associated with POLR2E,IL18, MAVS, and FADD expression.Conclusions: In summary, we present and validated a CDSRGs risk model that is an independent prognostic factor and indicates the immune characteristics of PC. This prognostic model may facilitate the personalized treatment and monitoring.

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The Mitochondrial Protein MAVS Stabilizes p53 to Suppress Tumorigenesis

Cited by 23 publications

References 43 publications

The role of ubiquitination and deubiquitination in cancer metabolism

The role of ubiquitination and deubiquitination in cancer metabolism

The Critical Role Played by Mitochondrial MITF Serine 73 Phosphorylation in Immunologically Activated Mast Cells

A Novel Prognostic Model Based On Cytosolic DNA Sensing-Related Gene Signature for Pancreatic Cancer

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