Video Experimental Relacionado
Updated: Feb 25, 2026
11:44
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
12.6K
La metilación de STAT1 mediada por la metiltransferasa SETD2 es crítica para la actividad antiviral del interferón
Kun Chen1, Juan Liu2, Shuxun Liu2
1Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Cell
|July 29, 2017
Resumen
El modificador epigenético SETD2 amplifica la inmunidad antiviral al interferón-α (IFNα) mediante la metilación de STAT1 y la promoción de los genes estimulados por IFN (ISG). La pérdida de SETD2 aumenta la infección por el virus de la hepatitis B (VHB), destacando la SETD2.
Área de la Ciencia:
- Inmunología
- La epigenética
- Hepatología
Sus antecedentes:
- La señalización de interferón-α (IFNα) es crucial para la defensa antiviral a través de los genes estimulados por IFN (ISG).
- La replicación del virus de la hepatitis B (VHB) puede ser inhibida por IFNα, pero los mecanismos epigenéticos subyacentes no se comprenden completamente.
Objetivo del estudio:
- Identificar los modificadores epigenéticos que regulan la inmunidad antiviral mediada por IFNα contra el VHB.
- Aclarar los mecanismos moleculares por los cuales SETD2 influye en la señalización de IFNα y la replicación del VHB.
Principales métodos:
- Cribado de RNAi de alto rendimiento de 711 modificadores epigenéticos en células tratadas con IFNα.
- Análisis de la replicación del VHB en ratones con knockout condicional Setd2.
- Ensayos bioquímicos para evaluar la metilación de STAT1 y la trimetilación de H3K36.
Principales resultados:
- Se identificó a SETD2 como un amplificador clave de la inmunidad antiviral IFNα.
- La deleción de Setd2 específica de los hepatocitos en ratones condujo a un aumento de la infección por el VHB.
- SETD2 metila directamente STAT1 en la lisina 525, mejorando la fosforilación de STAT1 y las respuestas antivirales.
- SETD2 cataliza la trimetilación de H3K36 en los promotores de ISG, promoviendo la activación del gen.
Conclusiones:
- La metilación de STAT1 por SETD2 es esencial para la inmunidad antiviral dependiente de IFNα.
- SETD2 juega un papel crítico en el control de las infecciones virales, particularmente el VHB.
- SETD2 representa un objetivo terapéutico potencial para el tratamiento de la hepatitis viral.
Videos de Conceptos Relacionados
01:20The JAK-STAT Signaling Pathway
13.3K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
13.3K
02:30siRNA - Small Interfering RNAs
18.8K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
18.8K
01:52Eukaryotic Transcription Inhibitors
11.1K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.1K
02:23Master Transcription Regulators
7.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.9K
02:04Covalently Linked Protein Regulators
9.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.8K
01:17Phase II Reactions: Methylation Reactions
808
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
808