ASCC3 review notes
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ASCC3 has separable nuclear DNA alkylation repair and cytosolic hRQT ribosome-rescue roles, and the PN GO:0006515 projection was not added because more specific RQC terms are already present.
"Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`."
Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic Gene Ontology annotation based on Rhea mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
Novel transcription coactivator complex containing activating signal cointegrator 1.
Defining the membrane proteome of NK cells.
DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation.
The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
Architecture of the human interactome defines protein communities and disease networks.
Ubiquitination of stalled ribosome triggers ribosome-associated quality control.
A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair.
RNA ligase-like domain in activating signal cointegrator 1 complex subunit 1 (ASCC1) regulates ASCC complex function during alkylation damage.
Identification of a novel trigger complex that facilitates ribosome-associated quality control in mammalian cells.
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The human RQT complex contains ASCC3, ASCC2, and TRIP4 and triggers RQC.
"The hRQT complex is composed of ASCC3, ASCC2, and TRIP4"
The ASC-1 Complex Disassembles Collided Ribosomes.
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ASCC disassembles ubiquitinated collided ribosomes, defining ASCC3 as a core RQC ribosome-rescue factor.
"ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome"
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation.
Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex.
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ASCC3 contains two tandem Ski2-like NTPase/helicase cassettes that cooperate to thread substrate through both cassettes, and TRIP4 docks via a zinc-finger domain to position an ASCH domain next to the C-terminal cassette and stimulate the helicase.
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TRIP4 and the dealkylase ALKBH3 bind ASCC3 in a mutually exclusive manner, providing a mechanism that directs ASCC3 toward distinct cellular processes.
The ASC-1 complex promotes translation initiation by scanning ribosomes.
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ASCC3 associates with scanning ribosomes and localizes predominantly to 5' untranslated regions, and its knockdown impairs 43S preinitiation complex loading and scanning dynamics, reducing translation efficiency for a subset of transcripts.
ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3.
Ribosomal collision is not a prerequisite for ZNF598-mediated ribosome ubiquitination and disassembly of ribosomal complexes by ASCC.
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After ZNF598-dependent K63-polyubiquitination of uS10, ASCC efficiently disassembles polysomal, monosomal, 80S elongation and 48S initiation complexes without a strict requirement for ribosomal collision, provided at least ~30-35 nucleotides of 3' mRNA remain downstream of the P site.
Case report: Second report of neuromuscular syndrome caused by biallelic variants in ASCC3.
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Biallelic loss-of-function variants in ASCC3 cause an autosomal-recessive neurodevelopmental and neuromuscular syndrome (MIM:620700) featuring global developmental delay, intellectual disability, reduced muscle tone and motor and language impairment.
Multimodal cell maps as a foundation for structural and functional genomics.
Oxidative demethylation of 1-meA damaged DNA By ALKBH3
Oxidative demethylation of 3-meC damaged DNA By ALKBH3
Oxidative dealkylation of 1-EtA damaged DNA by ABH3
ALKBH3 associated with ASCC1:ASCC2:ASCC3 binds alkylated dsDNA containing 3-meC
ALKBH3 associated with ASCC1:ASCC2:ASCC3 binds alkylated dsDNA containing 1-meA
ALKBH3 in complex with ASCC1:ASCC2:ASCC3 binds alkylated DNA containing 1-etA
RQT complex binds K63polyUb-80S ribosome:no-go mRNA:peptidyl-tRNA with nascent peptide
Ribosome-associated quality control
RQT complex:K63polyUb-80S ribosome dissociates yielding K63polyUb-40S subunit and 60S subunit:peptidyl-tRNA with nascent peptide