Parafibromin participates in the nuclear PAF1 transcription machinery. Its central role is to connect transcription with the factors that handle the emerging RNA. Human purification and reconstitution establish complex membership and association with RNA polymerase II; they do not isolate a purified human CDC73–PolII interface. The early primary report describes parafibromin as “part of a human Paf1 complex” (PMID:15632063(https://pubmed.ncbi.nlm.nih.gov/15632063/)). In the later reconstitution study, PAF1 and LEO1 provide the strongest measured PolII contacts; yeast CDC73 results are distinct from human subunit experiments (PMID:20178742(https://pubmed.ncbi.nlm.nih.gov/20178742/)).
CDC73 associates with CPSF/CstF and promotes their recruitment at a tested endogenous locus. Immunodepletion also removes processing factors, so that experiment alone cannot identify CDC73 as a core cleavage factor (PMID:19136632(https://pubmed.ncbi.nlm.nih.gov/19136632/)). The follow-up distinguishes transcription-coupled processing from an uncoupled RNA-substrate assay; direct VP16 binding belongs to PAF1 (PMID:21329879(https://pubmed.ncbi.nlm.nih.gov/21329879/)). The core therefore records binding and positive regulation of elongation/processing, without assigning RNA cleavage, poly(A) polymerase, ubiquitin-ligase or histone-methyltransferase activity to CDC73. No NEW annotation was needed.
Beta-catenin binding supports a more informative refinement of its corresponding generic interaction (PMID:16630820(https://pubmed.ncbi.nlm.nih.gov/16630820/)). KMT2A binding is likewise refined using the enzyme partner’s identity and the inspected interaction experiments; KMT2A catalysis remains distinct from CDC73 binding (PMID:20541477(https://pubmed.ncbi.nlm.nih.gov/20541477/)). PAF1C effects on myeloid differentiation include complex overexpression in human THP-1 cells, rather than a demonstrated isolated-subunit developmental mechanism.
Growth effects depend on context. The original G1/S study reports increased S phase after CDC73 depletion, so its positive-regulation source annotation is refined to negative regulation (PMID:15923622(https://pubmed.ncbi.nlm.nih.gov/15923622/)). MYC promoter and proliferation assays support secondary regulatory effects in HeLa and primary human dermal fibroblasts; the CDC73-knockdown MYC half-life increase is a nonsignificant trend, and depletion can also reduce other PAF1C components (PMID:18987311(https://pubmed.ncbi.nlm.nih.gov/18987311/)). Mouse stem-cell observations remain explicitly orthology-based. The LPS-transfer assertions are marked over-annotated after separating expression induction from functional participation (PMID:19345177(https://pubmed.ncbi.nlm.nih.gov/19345177/), PMID:17911113(https://pubmed.ncbi.nlm.nih.gov/17911113/)). The precise endodermal-fate experiment remains unresolved.
RTF1 association depends on preparation and assay. PMID:16024656 reports substoichiometric coimmunoprecipitation despite its absence from the stable purified core; PMID:20178742 supplies later complex evidence and documents partial dissociation during gel filtration. These source-specific results are distinguished below. The exact telomeric PICh target entry and unqualified SHP2 source assignment remain open. The exact Q06124-2 association is retained only at the demonstrated substrate-trapping mutant scope. Negative recovery in one assay does not prove absence of a transient physiological interaction.
The interaction evidence extract preserves source-linked pair IDs, taxa, assay methods, construct features and record URLs. Curated IntAct/BioGRID records establish the target-to-source linkage at their stated resolution; they are not independent replications of the underlying experiments. Affinity capture can recover an indirect complex. Expression hosts are not substituted for protein species, and mutation comparisons are not silently described as unqualified wild-type binding. The original supporting accessions and qualifiers remain unchanged.
The applicable immutable project curation instruction explicitly prefers “KEEP_AS_NON_CORE” for supported generic binding when a more informative MF is not justified. The review follows that instruction, uses specific binding terms where warranted, and leaves unresolved assertions UNDECIDED.
Source access was manual. The normal pipeline retrieved UniProt, GOA, publications and Reactome entries; genuine Falcon and explicit perplexity-lite attempts both timed out without producing a report. Abstract-only cache status is distinguished from selected external full-primary access for 15923622, 19136632 and 18987311. A full cache does not imply that every supplement or figure was inspected. Normal source files and original assertions were preserved. Independent annotation/core and interaction consultations informed the bounded judgments above.
The review retains all 127 source assertions, evidence codes, qualifiers, partner accessions and original citations. The 128 GOA rows contain one duplicate GO:0006368/IDA/PMID:20178742 assertion attributed by two providers; the normal seed represents it once. No new annotation was introduced.
Cell-cycle direction and protein stability. Short cache-verifiable excerpts now anchor the G1/S direction correction to PMID:15923622 and its independent human follow-up, PMID:18987311. The full latter paper distinguishes CDC73's nonsignificant MYC half-life comparison from the significant PAF1 result. The destabilization annotation is therefore marked over-annotated; this does not negate the paper's supported transcriptional and proliferation observations or prove a zero biological effect.
LPS and IL-6 contexts. The full original PMID:17911113 article, Results/Figures 1B, 2B and 4C/E, distinguishes mouse expression induction from human chromatin occupancy. Following negative LPS-alone tests, inflammatory assays use IL-6 plus soluble receptor; perturbation targets CTR9. The two human transfers therefore overstate CDC73-specific LPS function. The Q8JZM7 IDA provenance and normal abstract cache remain unchanged.
RTF1 source specificity. The full primary PMID:16024656 Results distinguish stable purification from coimmunoprecipitation: antibodies to PolII and RTF1 “coimmunoprecipitated substoichiometric amounts of each other” together with PAF1C subunits. This is the Results text describing Supplementary Figure 4; the image itself was not newly inspected. It supports a complex-associated interaction without proving a purified binary CDC73–RTF1 interface. The separate PMID:15923622 row explicitly retains its unresolved source-specific recovery and the independent PMID:20178742 corroboration. Negative recovery in one purification is not evidence that the interaction is biologically absent.
Wnt core synthesis. The PMID:16630820 primary abstract explicitly reports human parafibromin, direct beta-catenin binding and Wnt transcriptional activation, alongside distinct fly Hyrax experiments. This supplies a molecular coactivator role, so beta-catenin binding and the existing positive-Wnt IDA are now represented together as a second core function. The existing human CDC73 phosphosite-mutant comparison in PMID:29774127 is corroborating association evidence, with its construct limits retained. Neither Wnt activation nor the binding term is a new annotation.
Repeated optional reference-assessment boilerplate has been removed; the decisive sources above receive individual access and claim assessments. Machine-fetched reference identities and protected source caches are unchanged. The linked interaction JSON remains a machine-derived retrieval receipt with exact source pair identifiers and response hashes, rather than an authored model or independent biological replication.