Mass spectrometry raw data of U87 infected with HSV-1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Jun Cui
PROVIDER: PXD039377 | iProX | Thu Jan 12 00:00:00 GMT 2023
REPOSITORIES: iProX
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2014-09-27 | E-GEOD-61817 | biostudies-arrayexpress
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the host–virus dependencies are vital for the identification and rational design of effective antiviral therapy. Here, we report the dominant SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) through a proteome-wide protein interaction analysis. We further demonstrate that E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. Pharmacological intervention of ACE2 SUMOylation blocks the entry of SARS-CoV-2 and viral infection-triggered immune responses. Collectively, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination can be targeted to future antiviral therapy of SARS-CoV-2.
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Project description:Brain glia cells exhibit highly heterogeneity which can modify their genetic landscape and responding sensitivity, thus achieving appropriate responses to environmental changes for maintenance of CNS homeostasis. However, technical restriction has prevented the study on the self-orchestrating activity of CNS resident immune cells. Microglia and astrocytes are predominant responding cells at early stages during CNS viral infection. Their activation not only contributes to the recruitment of peripheral immune cells that aid in viral clearance, but also increases the risk of long-term detrimental inflammatory injury associated with many neurodegenerative diseases. Optimal autophagic activity is vital to maintain brain integrity, yet the autophagy regulation of immune activity in brain glia cells remains poorly understood. Here, we identify the membrane protein SHISA9 as an autophagy cargo receptor that modulates the heterogenic immune responses during CNS infection. By 10x single-cell RNA sequencing, we identify the astrocytes with increased Shisa9 expression followed by decreased expression of inflammatory transcriptional programs. Shisa9 has temporal characteristics in modulating both antiviral and inflammatory responses in microglia and astrocytes at different stages during infection. Shisa9-/- mice are highly susceptible to herpes simplex virus encephalitis, accompanied by higher rates of pathogenic astrocytes which might contribute to neurodegeneration progression and display a more severe neuroinflammation symptoms compared to wild-type mice. Taken together, our study unravels a critical role of selective autophagy in orchestrating immune heterogeneity of different CNS resident cells through SHISA9-IKKi axis.
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2011-09-30 | E-GEOD-32491 | biostudies-arrayexpress
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Project description:Autophagy is an evolutionally conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis1-3. Its acute regulation by nutrient sensing signaling pathways is well described, but its longer-term transcriptional regulation is not. The nuclear receptors PPARα and FXR are activated in the fasted or fed liver, respectively4,5. Here we show that both regulate hepatic autophagy. Pharmacologic activation of PPARα reverses the normal suppression of autophagy in the fed state, inducing autophagic lipid degradation, or lipophagy. This response is lost in PPARα knockout (PPARα-/-) mice, which are partially defective in the induction of autophagy by fasting. Pharmacologic activation of the bile acid receptor FXR strongly suppresses the induction of autophagy in the fasting state, and this response is absent in FXR knockout (FXR-/-) mice, which show a partial defect in suppression of hepatic autophagy in the fed state. PPARα and FXR compete for binding to shared sites in autophagic gene promoters, with opposite transcriptional outputs. These results reveal complementary, interlocking mechanisms for regulation of autophagy by nutrient status.
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