The coevolution between APOBEC3 and retrotransposons in primates

Modenini, Giorgia; Abondio, Paolo; Boattini, Alessio

doi:10.1186/s13100-022-00283-1

Cited by 3 publications

(3 citation statements)

References 147 publications

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“…In addition, evolutionary analyses of APOBEC3 proteins indicate that they have been under strong selective pressure over the last 30 million years. Additionally, polymorphisms have been found that contribute significantly to their antiviral efficacy [ 45 , 46 , 47 ].…”

Section: Apobec Proteins and Their Role In Viral Inhibition And Genom...mentioning

confidence: 99%

“…Traces of APOBEC mutations have been identified in the genomes of vertebrates, implying that APOBECs were important players in the restriction of retroelements and influenced their evolution [ 15 , 45 , 49 ]. Similar to the editing-independent inhibition of viral replication [ 50 ], the restriction of retrotransposition could also be editing-independent [ 14 , 46 , 49 , 51 , 52 ].…”

Section: Apobec Proteins and Their Role In Viral Inhibition And Genom...mentioning

confidence: 99%

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The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses

Lovšin,

Gangupam,

Bergant Marušič

2024

Pathogens

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APOBEC3 proteins are cytidine deaminases that play a crucial role in the innate immune response against viruses, including DNA viruses. Their main mechanism for restricting viral replication is the deamination of cytosine to uracil in viral DNA during replication. This process leads to hypermutation of the viral genome, resulting in loss of viral fitness and, in many cases, inactivation of the virus. APOBEC3 proteins inhibit the replication of a number of DNA tumour viruses, including herpesviruses, papillomaviruses and hepadnaviruses. Different APOBEC3s restrict the replication of different virus families in different ways and this restriction is not limited to one APOBEC3. Infection with DNA viruses often leads to the development and progression of cancer. APOBEC3 mutational signatures have been detected in various cancers, indicating the importance of APOBEC3s in carcinogenesis. Inhibition of DNA viruses by APOBEC3 proteins appears to play a dual role in this process. On the one hand, it is an essential component of the innate immune response to viral infections, and, on the other hand, it contributes to the pathogenesis of persistent viral infections and the progression of cancer. The current review examines the complex interplay between APOBEC3 proteins and DNA viruses and sheds light on the mechanisms of action, viral countermeasures and the impact on carcinogenesis. Deciphering the current issues in the interaction of APOBEC/DNA viruses should enable the development of new targeted cancer therapies.

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Section: Apobec Proteins and Their Role In Viral Inhibition And Genom...mentioning

confidence: 99%

Section: Apobec Proteins and Their Role In Viral Inhibition And Genom...mentioning

confidence: 99%

The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses

Lovšin,

Gangupam,

Bergant Marušič

2024

Pathogens

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“…And in reference to immune strategies to treat cancer, activation of LINE1 transcription has been shown to be a major mechanism of T cell exhaustion [89]. In response to transposon infection, particularly that of LINE1, primates also underwent a rapid expansion of the APOBEC3 family of cytosine deaminases which degrade transposons by inducing mutations in them [90]. Yet another mechanism of transposon suppression involves a family of zinc finger proteins that bind as transcription factors to methylated CpGs and play a critical role in gene regulation.…”

Section: Emergence Of Transposons Within the Primate Genome Coincides...mentioning

confidence: 99%

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

Nyce¹

2023

Preprint

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Adrenarche is a developmental phase that occurs only in humans and chimpanzees. It is characterized by the maturation of the adrenal zona reticularis, culminating in the synthesis and secretion of enormous amounts of dehydroepiandro-sterone sulfate (DHEAS) into the blood stream. The purpose of adrenarche, and the flooding of the circulation with DHEAS in the period preceding the onset of adult human body size, has been described as “enigmatic.” This laboratory has uncovered a previously unknown, human-specific “kill-switch” tumor suppression mechanism in which circulating DHEAS is pumped into cells that have undergone tumorigenic mutation(s)— primarily in the TP53 tumor suppressor gene. We refer to such tumorigenic single cells as singularities. The advantage of eliminating tumorigenic cells while they are still in their single cell state, before they have evolved into the heterogeneous tumor cell populations that have proven refractory to chemotherapeutic sterilization, is obvious. This is accomplished by activation of the kill-switch in singularities by de-sulfating imported DHEAS to dehydroepiandrosterone (DHEA), a potent uncompetitive inhibitor of the enzyme Glucose-6-phosphate Dehydrogenase (G6PD). G6PD is responsible for the production of most of the NADPH required for the synthesis and maintenance of activity of anti-oxidant selenoproteins, and for the ubiquinol that prevents ferroptosis. In singularities, uncompetitive inhibition of G6PD by DHEA rapidly becomes irreversible, leading to ROS/ferroptosis-mediated cell death.

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The Mechanism of APOBEC3B in Hepatitis B Virus Infection and HBV Related Hepatocellular Carcinoma Progression, Therapeutic and Prognostic Potential

Yang,

Wang,

2024

IDR

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Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors globally. Prominent factors include chronic hepatitis B (CHB) and chronic hepatitis C (CHC) virus infections, exposure to aflatoxin, alcohol abuse, diabetes, and obesity. The prevalence of hepatitis B (HBV) is substantial, and the significant proportion of asymptomatic carriers heightens the challenge in diagnosing and treating hepatocellular carcinoma (HCC), necessitating further and more comprehensive research. Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC) family members are single-stranded DNA cytidine deaminases that can restrict viral replication. The APOBEC-related mutation pattern constitutes a primary characteristic of somatic mutations in various cancer types such as lung, breast, bladder, head and neck, cervix, and ovary. Symptoms in the early stages of HCC are often subtle and nonspecific, posing challenges in treatment and monitoring. Furthermore, this article primarily focuses on the established specific mechanism of action of the APOBEC3B (A3B) gene in the onset and progression of HBV-related HCC (HBV-HCC) through stimulating mutations in HBV, activating Interleukin-6 (IL-6) and promoting reactive oxygen species(ROS) production, while also exploring the potential for A3B to serve as a therapeutic target and prognostic indicator in HBV-HCC.

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The coevolution between APOBEC3 and retrotransposons in primates

Cited by 3 publications

References 147 publications

The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses

The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

The Mechanism of APOBEC3B in Hepatitis B Virus Infection and HBV Related Hepatocellular Carcinoma Progression, Therapeutic and Prognostic Potential

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