CDKN1C/p57 is a CIP/Kip cyclin-dependent kinase inhibitor. The representative core is nuclear CDK inhibition coupled to restraint of the mitotic cell cycle. The biochemical source describes p57 as intrinsically disordered [PMID:11746698, "largely unfolded"]. The foundational study reports cyclin-dependent binding and G1 arrest; its complete Methods were not recovered. The current interpretation does not borrow a p27 crystal structure to assert an atomic p57 ATP-blocking mechanism. Full Results/Methods in PMID:19170105(https://pmc.ncbi.nlm.nih.gov/articles/PMC2981436/) independently compare human and mouse p57, cyclin-binding mutants, CDK2/histone-H1 kinase output and NPAT phosphorylation. The human WI38 reporter and HeLa depletion experiments are distinct from Cos7 overexpression and mouse MEF experiments.
Human genetics requires opposite disease mechanisms. The IMAGe source supports increased growth suppression [PMID:22634751, "suggesting a gain-of-function mechanism"]. Its human FLAG-CDKN1C/PCNA co-IP and Drosophila expression experiments are different assays. Wild-type p57 co-precipitates endogenous PCNA, whereas tested IMAGe alleles disrupt association; the study does not directly establish every downstream effect of changed ubiquitination or protein stability. BWS loss of function should not be assigned to IMAGe. Predominantly maternal expression is a property of the imprinted locus, not evidence that p57 protein creates that imprint.
The frozen GOA source fields, literal mouse-donor joins and exact interaction identifiers are available in CDKN1C-source-evidence.json. This retains all 37 original source assertions and the original gene product. The historical review lacks explicit qualifier/partner slots, so the immutable GOA fields are supplied as provenance without rewriting the source YAML. The two PAINT nodes were not independently reconstructed; human self-evidence in the epithelial-proliferation IBA is legitimate descendant evidence, not circularity. The campaign binding instruction at the pinned main commit retains supported generic binding as non-core when no better supported activity is established.
The electronic mouse transfers were traced to experimental records rather than inferred from the donor identifier alone. PMID:19276117(https://pmc.ncbi.nlm.nih.gov/articles/PMC2664003/) directly compares p57-null and p27-knock-in mice: most skeletal, lens, intestinal, growth and reproductive defects improve; renal and placental abnormalities persist with altered expression patterns. These support contextual developmental roles, while the experiments do not isolate a single mechanism for every organ. PMID:21729874(https://pmc.ncbi.nlm.nih.gov/articles/PMC3209650/) directly examines mutant placental architecture and stage-dependent growth, with explicit mouse strain and intrauterine-competition limits.
PMID:9784491(https://pmc.ncbi.nlm.nih.gov/articles/PMC317217/) compares p57/p27 mutant lens and placenta with BrdU, differentiation markers and histology. These assays establish restraint of cycling during differentiation, rather than the anaphase/telophase-to-G1 transition in GO:0007096. Its source-specific replacement is the existing negative-mitotic-cell-cycle term; no NEW process is proposed. The p27 replacement experiment in PMID:19276117 retains maternal-allele expression at the p57 locus. It does not show p57 protein establishing or propagating epigenetic imprints, so the genomic-imprinting protein annotation is removed on that specific source premise.
PMID:14671317(https://pmc.ncbi.nlm.nih.gov/articles/PMC307617/) examines mouse dopamine-neuron maturation and Nurr1 cooperation in MN9D cells. CDK-defective p57 retains cooperative maturation activity, and Nurr1 reporter suppression is promoter-context dependent. PMID:15889154(https://pmc.ncbi.nlm.nih.gov/articles/PMC1142590/) Figure 6 directly tests mouse-p57 adenoviral rescue of MBT-1-deficient myeloid progenitors; human TF-1 expression kinetics are separate corroboration. Both existing developmental annotations are retained outside the representative core.
PMID:20106982(https://pmc.ncbi.nlm.nih.gov/articles/PMC2843230/) supports transcriptional regulation but requires assay distinctions: Ad-p57 expresses mouse cdkn1c, whereas endogenous HeLa depletion independently affects CTD phosphorylation. Kinase experiments use immunopurified cellular complexes, and bacterial E2F1 binding assays use crude lysates. Neither experiment establishes sequence-specific DNA binding by p57. The specific RNAPII transcriptional process is retained as contextual; a second vague inhibitor core is unnecessary.
In PMID:16943770(https://pmc.ncbi.nlm.nih.gov/articles/PMC2906388/), p57 is induced by TGF-beta and p57 depletion restores human limbal-cell BrdU/MTT proliferation. This directly supports downstream antiproliferative participation. It does not distinguish that from increased signaling propagation or feedback, so the positive-pathway-regulation specificity is marked over-annotated. Positive feedback could act downstream of the receptor; its existence is not excluded. Nuclear and cytoplasmic localization are retained, with the nucleus as the principal functional setting.
The full main text was genuinely read externally for 18660753, 16943770, 19276117, 9784491 and 20106982. Indexed primary full Methods/selected Results were read for 14671317 and 15889154 even though direct local downloads met challenges. A fresh normal full-text variant supplied the missing 19170105 Methods/Results; the existing main cache is preserved. Normal caches for 22634751, 28425505 and 21729874 include the inspected full sections. Original main caches and genuine historical provider reports remain unchanged. The fresh Falcon attempt timed out and the explicit Perplexity fallback failed with insufficient quota; no new provider report was fabricated. These dated notes document the manual audit.
The remaining UNDECIDED MCM7 association requires its actual target assay. This limitation does not negate the independently demonstrated CDK-inhibitor function. No NEW annotation or automatic source refresh is included.
The GO:0044877 annotation is now ACCEPT. Its original IPI source is PMID:11746698, with ComplexPortal:CPX-2006 recorded in the unchanged source extract. The official complex record identifies the human CCNA2–CDK2 complex (P20248/P24941); the GO definition covers binding to a macromolecular complex. This interaction is part of p57's principal inhibitor function. Replacing it with an already represented inhibitor annotation unnecessarily discarded the binding fact. The existing inhibitor core and three inhibitor annotations are retained. The campaign instruction for generic GO:0005515 does not require replacing this distinct complex-binding term.
The authentic PMID:11746698 abstract reports cyclin A–CDK2 inhibition by p57 and by its N-terminal domain. The publisher's full article and PDF again returned access challenges; no newly inspected binding Methods or construct-species details are claimed. Retaining the specific experimental curator assertion is consistent with the independently established inhibitor role and the absence of contrary evidence. All original source fields and the original source extract remain unchanged.
A suggested question now asks for upstream review of the mouse P49919 genomic-imprinting annotation from PMID:19276117. This follows the already documented coding-replacement experiment and distinguishes an imprinted locus from an imprint-establishing protein activity; it adds no annotation. All other decisions, reference assessments and core terms remain unchanged. The earlier notes are retained verbatim above.