-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Natural immunity is the body's "first line of defense"
against pathogen invasion.
When pathogens such as viruses invade, their nucleic acid molecules (DNA and RNA) are red flags in cells and stimulate the body to activate its natural immune defenses
.
Cyclic guanylate-adenylate synthase (cGAS) was discovered by Professor Chen Zhijian of the University of Texas Southwestern Medical Center in 2013 and has become a research hotspot
in the field of natural immunity in recent years.
cGAS can recognize double-stranded DNA molecules of pathogens and is one of
the important "sentinels" that activate the natural immune defense against viruses.
In addition to fighting viral infections, cGAS-mediated natural immune signaling pathways also play an important role
in the occurrence of diseases such as tumor immunity and autoinflammation.
Defects or abnormal activation of cGAS function can cause the body's immune balance to be imbalanced, resulting in viral infection or autoimmune diseases
.
Therefore, it is of great significance
to explore the mechanism of cGAS function regulation.
Recently, Yin Hang's research group at the School of Pharmacy of Tsinghua University published a paper in the journal Nucleic Acids Research entitled "USP15 promotes cGAS activation through deubiquitylation and" Research paper
on liquid condensation.
The novelty of this study is that the discovery of deubiquitinase USP15, as an interacting protein of cGAS, jointly promotes the activation of cGAS-mediated natural immune signaling pathways through deubiquitination and phase separation, which provides a new idea
for the development of cGAS-targeted antiviral drugs.
This study identified USP15 as an interactive protein of cGAS through co-immunoprecipitation and protein mass spectrometry, and that USP15 can promote cGAS recognition of DNA to activate downstream signaling pathways
。 The expression of USP15 is regulated by double-stranded DNA in the cytoplasm, and in macrophages with deletion of USP15 gene, DNA loses the ability to activate natural immune signaling pathways, indicating that USP15 promotes the activation
of DNA-induced natural immune signaling pathways in a positive feedback manner.
This phenotype is achieved by USP15 through two molecular mechanisms: first, USP15 can enhance cGAS activity by hydrolyzing multiple types of ubiquitination modifications of cGAS; Second, USP15 can promote the phase separation structure formed by cGAS and DNA, and promote the binding
of cGAS to DNA.
The above two mechanisms are parallel to each other and jointly promote the activation
of cGAS.
USP15-mediated process of cGAS deubiquitination modification and enhanced phase separation promotes DNA-induced native immune signaling, revealing novel microregulatory mechanisms
in native immune pathways.
The deubiquitinase USP15 can either activate cGAS in the form of deubiquitination and promote the binding
of cGAS and DNA by phase separation.
In cells, USP15 acts as a signal amplifier in the process of DNA activation of cGAS in this positive feedback manner, which enables the rapid activation of natural immune signaling pathways, revealing a new fine regulation mechanism
of natural immune signaling.
The first author of the paper is Shi Chengrui, a postdoctoral fellow at the School of Pharmacy, Tsinghua University, and the co-first author is Yang Xikang
, a doctoral student in the Department of Chemistry, Tsinghua University.
The corresponding author is Professor
Yin Hang, School of Pharmacy, Tsinghua University.
The research was supported
by the Advanced Innovation Center for Structural Biology of Tsinghua University, the Joint Center for Life Sciences, the National Natural Science Foundation of China, the Beijing University Outstanding Young Scientists Program and the Beijing Natural Science Foundation of China.
Link: https://doi.
org/10.
1093/nar/gkac823
open for reprinting Welcome to forward to Moments and WeChat groups
against pathogen invasion.
When pathogens such as viruses invade, their nucleic acid molecules (DNA and RNA) are red flags in cells and stimulate the body to activate its natural immune defenses
.
Cyclic guanylate-adenylate synthase (cGAS) was discovered by Professor Chen Zhijian of the University of Texas Southwestern Medical Center in 2013 and has become a research hotspot
in the field of natural immunity in recent years.
cGAS can recognize double-stranded DNA molecules of pathogens and is one of
the important "sentinels" that activate the natural immune defense against viruses.
In addition to fighting viral infections, cGAS-mediated natural immune signaling pathways also play an important role
in the occurrence of diseases such as tumor immunity and autoinflammation.
Defects or abnormal activation of cGAS function can cause the body's immune balance to be imbalanced, resulting in viral infection or autoimmune diseases
.
Therefore, it is of great significance
to explore the mechanism of cGAS function regulation.
Recently, Yin Hang's research group at the School of Pharmacy of Tsinghua University published a paper in the journal Nucleic Acids Research entitled "USP15 promotes cGAS activation through deubiquitylation and" Research paper
on liquid condensation.
The novelty of this study is that the discovery of deubiquitinase USP15, as an interacting protein of cGAS, jointly promotes the activation of cGAS-mediated natural immune signaling pathways through deubiquitination and phase separation, which provides a new idea
for the development of cGAS-targeted antiviral drugs.
This study identified USP15 as an interactive protein of cGAS through co-immunoprecipitation and protein mass spectrometry, and that USP15 can promote cGAS recognition of DNA to activate downstream signaling pathways
。 The expression of USP15 is regulated by double-stranded DNA in the cytoplasm, and in macrophages with deletion of USP15 gene, DNA loses the ability to activate natural immune signaling pathways, indicating that USP15 promotes the activation
of DNA-induced natural immune signaling pathways in a positive feedback manner.
This phenotype is achieved by USP15 through two molecular mechanisms: first, USP15 can enhance cGAS activity by hydrolyzing multiple types of ubiquitination modifications of cGAS; Second, USP15 can promote the phase separation structure formed by cGAS and DNA, and promote the binding
of cGAS to DNA.
The above two mechanisms are parallel to each other and jointly promote the activation
of cGAS.
USP15-mediated process of cGAS deubiquitination modification and enhanced phase separation promotes DNA-induced native immune signaling, revealing novel microregulatory mechanisms
in native immune pathways.
The deubiquitinase USP15 can either activate cGAS in the form of deubiquitination and promote the binding
of cGAS and DNA by phase separation.
In cells, USP15 acts as a signal amplifier in the process of DNA activation of cGAS in this positive feedback manner, which enables the rapid activation of natural immune signaling pathways, revealing a new fine regulation mechanism
of natural immune signaling.
The first author of the paper is Shi Chengrui, a postdoctoral fellow at the School of Pharmacy, Tsinghua University, and the co-first author is Yang Xikang
, a doctoral student in the Department of Chemistry, Tsinghua University.
The corresponding author is Professor
Yin Hang, School of Pharmacy, Tsinghua University.
The research was supported
by the Advanced Innovation Center for Structural Biology of Tsinghua University, the Joint Center for Life Sciences, the National Natural Science Foundation of China, the Beijing University Outstanding Young Scientists Program and the Beijing Natural Science Foundation of China.
Link: https://doi.
org/10.
1093/nar/gkac823
open for reprinting Welcome to forward to Moments and WeChat groups
