Attenuation of Influenza a Virus into Live Vaccines Through C‐End Degrons
Naturally occurring C‐end degrons are exploited to design proteolysis‐targeting live attenuated influenza vaccines. C‐end degron tagging of viral M1 protein promotes proteasome‐dependent degradation, resulting in robust attenuation in host cells while permitting scalable production in engineered cells.
Ping Wang +14 more
wiley +1 more source
Lactylation‐Driven YTHDC1 Alleviates MASLD by Suppressing PTPN22‐Mediated Dephosphorylation of NLRP3
In MASLD, YTHDC1 undergoes increased lactylation and ubiquitination, reducing its expression. AARS1 mediates lactylation at lysine 565, while disrupted binding to LDHA further promotes lactylation, suppressing YTHDC1. This downregulation enhances PTPN22 mRNA stability, leading to NLRP3 dephosphorylation and activation, which exacerbates inflammation ...
Feng Zhang +16 more
wiley +1 more source
A Tyrosine Switch on NEDD4-2 E3 Ligase Transmits GPCR Inflammatory Signaling
Summary: Ubiquitination is essential for protein degradation and signaling and pivotal to many physiological processes. Ubiquitination of a subset of G-protein-coupled receptors (GPCRs) by the E3 ligase NEDD4-2 is required for p38 activation, but how ...
Neil J. Grimsey +10 more
doaj +1 more source
Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity [PDF]
MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in
A Plechanovová +71 more
core +1 more source
RNF213 is characterized as a dual‐functional antiviral effector. It directly mediates the degradation of the influenza A virus nucleoprotein (NP) while simultaneously activating the MDA5‐mediated innate immune signaling pathway. This coordinated response establishes a powerful host defense system against viral infection. ABSTRACT Influenza A virus (IAV)
Haoning Li +5 more
wiley +1 more source
RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain
Ubiquitin ligases play critical roles in neuronal connectivity in the brain. Here, Valnegri and colleagues show that ubiquitin ligase RNF8 and ubiquitin-conjugating enzyme UBC13 regulate synapse number in cerebellar granule neurons and rodent cerebellar ...
Pamela Valnegri +7 more
doaj +1 more source
LMO7 Suppresses Tumor‐Associated Macrophage Phagocytosis of Tumor Cells Through Degradation of LRP1
LMO7 in tumor‐associated macrophages suppresses phagocytosis of tumor cells and limits cytotoxic T lymphocytes infiltration, fostering tumor progression. Mechanistically, LMO7 mediates the ubiquitination and degradation of the phagocytic receptor LRP1, impairing its ability to engulf tumor cells and driving macrophages toward an antitumor phenotype ...
Mengkai Li +12 more
wiley +1 more source
XIAP Stabilizes DDRGK1 to Promote ER‐Phagy and Protects Against Noise‐Induced Hearing Loss
Mechanism of GAS‐mediated protection against noise‐induced hearing loss (NIHL). Noise exposure activates the ATF4/eIF2α axis, downregulating XIAP and promoting DDRGK1 degradation, thereby inhibiting ER‐phagy and leading to hair cell (HC) death. GAS treatment rescues XIAP and DDRGK1 expression, reactivating ER‐phagy to mitigate HC loss, synaptic damage,
Lin Yan +13 more
wiley +1 more source
BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase
The RING domain proteins BRCA1 and BARD1 comprise a heterodimeric ubiquitin (E3) ligase that is required for the accumulation of ubiquitin conjugates at sites of DNA damage and for silencing at DNA satellite repeat regions. Despite its links to chromatin,
Reinhard Kalb +4 more
doaj +1 more source
Biochemical and Genetic Studies of UBR3, a Ubiquitin Ligase with a Function in Olfactory and Other Sensory Systems [PDF]
Our previous work identified E3 ubiquitin ligases, termed UBR1-UBR7, that contain the ~70-residue UBR box, a motif important for the targeting of N-end rule substrates.
Hellweg, Rainer +6 more
core +1 more source

