O-GlcNAc modification regulates MTA1 transcriptional activity during breast cancer cell genotoxic adaptation

Xie, Xueqin; Wu, Qiutong; Zhang, Keren; Liu, Yimin; Zhang, Nana; Chen, Qiushi; Wang, Lingyan; Li, Wenli; Zhang, Jianing; Liu, Yubo

doi:10.1016/j.bbagen.2021.129930

Cited by 16 publications

(14 citation statements)

References 38 publications

(42 reference statements)

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“…Cancer cells also apply similar means to antagonize the genotoxicity from commonly used chemotherapeutic agents, such as adriamycin (adm) [ 126 ]. A study in breast cancer cells detected that MTA1, a highly deregulated oncogene involved in the stress adaptation of cancer, is an OGT substrate [ 127 , 128 ]. Intriguingly, MTA1 displayed enhanced interaction with OGT in adm-resistant (MCF7/ADR) cells compared to adm-sensitive (MCF7) cells [ 128 ].…”

Section: Dysregulated Protein Functions By Rewired Ogt/oga Protein Ne...mentioning

confidence: 99%

“…A study in breast cancer cells detected that MTA1, a highly deregulated oncogene involved in the stress adaptation of cancer, is an OGT substrate [ 127 , 128 ]. Intriguingly, MTA1 displayed enhanced interaction with OGT in adm-resistant (MCF7/ADR) cells compared to adm-sensitive (MCF7) cells [ 128 ]. Immunoprecipitation and genome-wide analysis further showed that O-GlcNAcylation of MTA1 promoted its association with components of nucleosome remodeling and histone deacetylation (NuRD) complex, including HDAC1, MBD3, and CHD4, and recruited MTA1 to the promoter of stress-adaptive genes for transcriptional activation.…”

Section: Dysregulated Protein Functions By Rewired Ogt/oga Protein Ne...mentioning

confidence: 99%

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The Emerging Roles of Protein Interactions with O-GlcNAc Cycling Enzymes in Cancer

Xie

Jiang

2022

Cancers

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The dynamic O-GlcNAc modification of intracellular proteins is an important nutrient sensor for integrating metabolic signals into vast networks of highly coordinated cellular activities. Dysregulation of the sole enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), and the associated cellular O-GlcNAc profile is a common feature across nearly every cancer type. Many studies have investigated the effects of aberrant OGT/OGA expression on global O-GlcNAcylation activity in cancer cells. However, recent studies have begun to elucidate the roles of protein–protein interactions (PPIs), potentially through regions outside of the immediate catalytic site of OGT/OGA, that regulate greater protein networks to facilitate substrate-specific modification, protein translocalization, and the assembly of larger biomolecular complexes. Perturbation of OGT/OGA PPI networks makes profound changes in the cell and may directly contribute to cancer malignancies. Herein, we highlight recent studies on the structural features of OGT and OGA, as well as the emerging roles and molecular mechanisms of their aberrant PPIs in rewiring cancer networks. By integrating complementary approaches, the research in this area will aid in the identification of key protein contacts and functional modules derived from OGT/OGA that drive oncogenesis and will illuminate new directions for anti-cancer drug development.

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Section: Dysregulated Protein Functions By Rewired Ogt/oga Protein Ne...mentioning

confidence: 99%

Section: Dysregulated Protein Functions By Rewired Ogt/oga Protein Ne...mentioning

confidence: 99%

The Emerging Roles of Protein Interactions with O-GlcNAc Cycling Enzymes in Cancer

Xie

Jiang

2022

Cancers

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“…MTA1 is another component of NuRD, which bridges NuRD complex and gene-specific transcription factors. MTA1 can be O-GlcNAcylated at serine S237/S241/S246 [ 192 ]. O-GlcNAcylation enhanced MTA1 association with the rest of NuRD complex.…”

Section: Regulation Of Epigenetic Machinery By O-glcnacylationmentioning

confidence: 99%

“…And promotes genome targeting of NuRD. In breast cancer cells, O-GlcNAcylation of MTA1 promotes the expression of genes involved in adaptation of breast cancer cells to genotoxic stress [ 192 ].…”

Section: Regulation Of Epigenetic Machinery By O-glcnacylationmentioning

confidence: 99%

O-GlcNAcylation links oncogenic signals and cancer epigenetics

Sun

Song

2021

Discov Onc

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Prevalent dysregulation of epigenetic modifications plays a pivotal role in cancer. Targeting epigenetic abnormality is a new strategy for cancer therapy. Understanding how conventional oncogenic factors cause epigenetic abnormality is of great basic and translational value. O-GlcNAcylation is a protein modification which affects physiology and pathophysiology. In mammals, O-GlcNAcylation is catalyzed by one single enzyme OGT and removed by one single enzyme OGA. O-GlcNAcylation is affected by the availability of the donor, UDP-GlcNAc, generated by the serial enzymatic reactions in the hexoamine biogenesis pathway (HBP). O-GlcNAcylation regulates a wide spectrum of substrates including many proteins involved in epigenetic modification. Like epigenetic modifications, abnormality of O-GlcNAcylation is also common in cancer. Studies have revealed substantial impact on HBP enzymes and OGT/OGA by oncogenic signals. In this review, we will first summarize how oncogenic signals regulate HBP enzymes, OGT and OGA in cancer. We will then integrate this knowledge with the up to date understanding how O-GlcNAcylation regulates epigenetic machinery. With this, we propose a signal axis from oncogenic signals through O-GlcNAcylation dysregulation to epigenetic abnormality in cancer. Further elucidation of this axis will not only advance our understanding of cancer biology but also provide new revenues towards cancer therapy.

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“…Therapeutic resistance of cancer is an important factor in contributing to the invasiveness and metastasis of cancer cells [167,168], which relies on escaping apoptosis and increasing drug efflux [169]. In recent years, several studies have focused on MTA1 as an important mediator of cancer therapeutic resistance [170][171][172][173][174]. Despite the fact that the role of MTA1 in therapeutic resistance has not been studied and discussed on HCC, these studies provide information about emerging functions and mechanisms of MTA1 in aggressive cancers.…”

Section: Therapeutic Significance Of Mta1mentioning

confidence: 99%

Molecular Mechanisms and Animal Models of HBV-Related Hepatocellular Carcinoma: With Emphasis on Metastatic Tumor Antigen 1

Liu

2021

IJMS

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Hepatocellular carcinoma (HCC) is an important cause of cancer death worldwide, and hepatitis B virus (HBV) infection is a major etiology, particularly in the Asia-Pacific region. Lack of sensitive biomarkers for early diagnosis of HCC and lack of effective therapeutics for patients with advanced HCC are the main reasons for high HCC mortality; these clinical needs are linked to the molecular heterogeneity of hepatocarcinogenesis. Animal models are the basis of preclinical and translational research in HBV-related HCC (HBV-HCC). Recent advances in methodology have allowed the development of several animal models to address various aspects of chronic liver disease, including HCC, which HBV causes in humans. Currently, multiple HBV-HCC animal models, including conventional, hydrodynamics-transfection-based, viral vector-mediated transgenic, and xenograft mice models, as well as the hepadnavirus-infected tree shrew and woodchuck models, are available. This review provides an overview of molecular mechanisms and animal models of HBV-HCC. Additionally, the metastatic tumor antigen 1 (MTA1), a cancer-promoting molecule, was introduced as an example to address the importance of a suitable animal model for studying HBV-related hepatocarcinogenesis.

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O-GlcNAc modification regulates MTA1 transcriptional activity during breast cancer cell genotoxic adaptation

Cited by 16 publications

References 38 publications

The Emerging Roles of Protein Interactions with O-GlcNAc Cycling Enzymes in Cancer

The Emerging Roles of Protein Interactions with O-GlcNAc Cycling Enzymes in Cancer

O-GlcNAcylation links oncogenic signals and cancer epigenetics

Molecular Mechanisms and Animal Models of HBV-Related Hepatocellular Carcinoma: With Emphasis on Metastatic Tumor Antigen 1

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