Affinage

CDC26

Anaphase-promoting complex subunit CDC26 · UniProt Q8NHZ8

Length
85 aa
Mass
9.8 kDa
Annotated
2026-04-28
27 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDC26 is a small, conserved subunit of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase that is essential for mitotic and meiotic cell cycle progression across eukaryotes. Structurally, CDC26 stabilizes the TPR-containing APC subunit APC6 (Cdc16) by forming an intermolecular TPR-mimic interaction, with its N-acetylated methionine buried within the APC6 TPR superhelix to protect CDC26 itself from Doa10-mediated proteasomal degradation (PMID:19668213, PMID:20924356). Loss of CDC26 impairs APC/C complex assembly and blocks cyclin proteolysis, causing mitotic arrest and, in vertebrates, apoptosis in dividing cells and improper cell cycle re-entry in quiescent cells (PMID:9348530, PMID:17141209). LATS1/2 kinases phosphorylate CDC26 at Thr7, reducing its interaction with APC6 and modulating APC/C assembly and substrate ubiquitination, including that of Plk1 (PMID:25723520).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1996 High

    Identification of CDC26 as a subunit of the yeast APC/C established that this small protein is a component of the multisubunit ubiquitin ligase required for anaphase entry and cyclin destruction.

    Evidence Biochemical purification and subunit identification of the 36S yeast APC particle

    PMID:8895471

    Open questions at the time
    • Molecular function of Cdc26 within the APC was unknown
    • No structural data on Cdc26 interaction with other subunits
  2. 1997 High

    Genetic and biochemical studies demonstrated that CDC26 mutations block mitotic cyclin (Clb2) proteolysis and that Cdc26 physically associates with APC subunits Cdc16, Cdc23, Cdc27, and Doc1, while fission yeast ortholog Hcn1 promotes APC complex assembly when overexpressed in cut9 mutants.

    Evidence Co-immunoprecipitation and sucrose gradient sedimentation in budding and fission yeast; genetic suppression of cut9 mutants

    PMID:9264466 PMID:9348530

    Open questions at the time
    • Whether Cdc26 directly contacts a single APC subunit or bridges multiple subunits was unresolved
    • Mechanism of Cdc26 contribution to APC assembly stability was unknown
  3. 1999 Medium

    Epistasis analysis placed CDC26-dependent APC activity in a specific mitotic checkpoint signaling branch (Bub2 pathway), distinguishing it from the Mad2-dependent branch.

    Evidence Double-mutant analysis (bub2 cdc26) with nocodazole treatment in budding yeast

    PMID:10352016

    Open questions at the time
    • Whether Cdc26 has a direct checkpoint signaling role or simply enables APC activity required downstream of Bub2
    • No biochemical link to checkpoint proteins
  4. 2000 High

    Mass spectrometric identification of CDC26 as a human APC subunit confirmed its evolutionary conservation from yeast to vertebrates.

    Evidence Mass spectrometry of purified human APC/C

    PMID:10922056

    Open questions at the time
    • Functional requirement of vertebrate CDC26 for APC/C activity was not yet tested
  5. 2006 Medium

    Vertebrate loss-of-function analysis in zebrafish and C. elegans revealed that CDC26 is essential for mitotic progression (causing arrest and apoptosis when absent) and also prevents improper cell cycle re-entry in post-mitotic cells, extending the functional requirement beyond cycling cells.

    Evidence Zebrafish genetic mutant analysis with live imaging; C. elegans RNAi with cross-species complementation of yeast cdc26Δ

    PMID:17141209 PMID:17374146

    Open questions at the time
    • Post-mitotic re-entry mechanism was not molecularly characterized
    • Whether CDC26 loss affects all APC/C substrates equally was untested
  6. 2009 High

    Crystal structures revealed that CDC26 stabilizes APC6 by forming an intermolecular TPR-mimic helix pair, and that the acetylated N-terminal methionine of CDC26 is buried within the APC6 TPR superhelix, protecting it from Doa10-mediated ubiquitin-dependent degradation — thus explaining the co-dependent stability of these two subunits.

    Evidence X-ray crystallography of human APC6-CDC26 and S. pombe Cut9-Hcn1 complexes; biophysical binding assays; genetic complementation

    PMID:19668213 PMID:20924356

    Open questions at the time
    • How CDC26-APC6 interaction is regulated in vivo was unknown
    • No structural information on CDC26 in the context of the full APC/C holocomplex at this time
  7. 2015 High

    Discovery that Hippo pathway kinases LATS1/2 phosphorylate CDC26 at Thr7, weakening its interaction with APC6 and thereby modulating APC/C complex assembly and substrate ubiquitination (including Plk1), established CDC26 as a regulated input connecting Hippo signaling to APC/C activity.

    Evidence In vitro kinase assays; phospho-mutant co-IP; gel filtration of APC/C; ubiquitination assays in HeLa cells

    PMID:25723520

    Open questions at the time
    • In vivo phosphorylation dynamics during mitosis not characterized
    • Whether LATS1/2 regulation of CDC26 affects all or selective APC/C substrates unclear
    • No structural view of how pThr7 disrupts APC6 binding
  8. 2021 Medium

    Demonstration that CDC26 declines in aged human oocytes and that its knockdown causes aneuploidy while overexpression partially rescues age-related meiotic defects identified CDC26 as a limiting factor for meiotic fidelity in mammalian oocytes.

    Evidence Single-cell RNA-seq; immunocytochemistry of human oocytes; mouse oocyte knockdown and lentiviral overexpression

    PMID:34590680

    Open questions at the time
    • Whether CDC26 decline is causal or correlative with broader APC/C deterioration in aging oocytes
    • Specific APC/C substrates misregulated in aged oocytes not identified
  9. 2025 Medium

    A study in pancreatic cancer cells reported that CDC26 promotes ferroptosis by facilitating ubiquitin-mediated degradation of SLC7A11, suggesting a non-canonical APC/C substrate connection to ferroptotic cell death.

    Evidence CDC26 overexpression/knockdown in pancreatic ductal adenocarcinoma cells; ubiquitination and lipid peroxidation assays

    PMID:41249642

    Open questions at the time
    • Whether SLC7A11 is a direct APC/C substrate or indirectly regulated remains unresolved
    • Single-lab finding not yet independently confirmed
    • APC/C dependence of the ferroptosis phenotype not formally tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include whether CDC26 phosphorylation by LATS1/2 is dynamically regulated during the cell cycle, whether CDC26 loss differentially affects specific APC/C substrates versus globally impairs activity, and how the CDC26-APC6 interaction is positioned within the fully assembled APC/C holocomplex in human cells.
  • No in vivo temporal mapping of CDC26 Thr7 phosphorylation across cell cycle phases
  • Substrate selectivity of CDC26-dependent APC/C activity not systematically addressed
  • Full reconstitution of CDC26-dependent APC/C assembly intermediates lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-392499 Metabolism of proteins 4
Partners
ANAPC5APC6CDC23CDC27LATS1LATS2
Complex memberships
APC/C

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 CDC26 (Cdc26p) was identified as a small heat-inducible subunit of the anaphase-promoting complex (APC/cyclosome) in Saccharomyces cerevisiae, a 36S particle containing at least seven proteins that functions as a cell cycle-regulated ubiquitin-protein ligase required for entry into anaphase and proteolysis of B-type cyclins. Biochemical purification and subunit identification of the yeast APC Science High 8895471
1997 Mutations in CDC26 prevent mitotic cyclin (Clb2) proteolysis, causing arrest as large-budded cells with high Clb2 levels; Cdc26 associates in vivo with Doc1, Cdc16, Cdc23, and Cdc27, and cosediments at 20S with Cdc27, confirming it is an APC component. Genetic screen for mitotic arrest mutants; in vivo co-immunoprecipitation; sucrose gradient sedimentation Molecular biology of the cell High 9348530
2000 CDC26 was mass-spectrometrically identified as a subunit of the human APC, confirming its conservation from yeast to vertebrates. Mass spectrometric identification of human APC subunits Proceedings of the National Academy of Sciences of the United States of America High 10922056
1997 In fission yeast, Hcn1 (the Cdc26 orthologue) can restore assembly of the 20S APC/cyclosome complex impaired in cut9 mutants when Hcn1 levels are elevated, indicating Cdc26/Hcn1 plays a role in APC complex assembly/stability. Genetic suppression; sucrose gradient sedimentation of the 20S complex Journal of cell science Medium 9264466
1999 Cell cycle progression of bub2 yeast cells treated with nocodazole requires the Cdc26 APC subunit, placing Cdc26 in a specific pathway branch of the mitotic checkpoint distinct from the Mad2 pathway. Genetic epistasis analysis using double mutants (bub2 cdc26) in the presence of nocodazole The Journal of cell biology Medium 10352016
2009 CDC26 stabilizes the structure of APC6 (a core TPR protein of the APC) through an intermolecular TPR mimic composed of one helix from each protein, as established by crystal structure and biophysical and genetic studies. Crystal structure determination; biophysical binding assays; genetic complementation Nature structural & molecular biology High 19668213
2010 Crystal structure of S. pombe Cut9 (Cdc16/Apc6) in complex with Hcn1 (Cdc26 orthologue) revealed that the C-terminal TPR block of Cut9 interacts with Hcn1, and that the acetylated N-terminal Met of Hcn1 is enclosed within the Cut9 TPR superhelix chamber, protecting Hcn1/Cdc26 from Doa10-mediated ubiquitin-dependent degradation. Crystal structure determination; structural analysis of N-acetyl-Met burial The EMBO journal High 20924356
2015 LATS1 and LATS2 directly phosphorylate the Thr7 residue of human CDC26; this phosphorylation reduces CDC26 interaction with APC6, alters APC/C assembly size, and promotes ubiquitination of polo-like kinase 1 (a CDC26-dependent APC/C substrate). In vitro kinase assay; knockdown in HeLa cells; co-immunoprecipitation with phospho-mutant CDC26; gel filtration; ubiquitination assay PloS one High 25723520
2007 The C. elegans gene B0511.9 encodes the CDC26 orthologue (CDC-26); strong RNAi knockdown causes embryonic arrest in metaphase of meiosis I, phenocopying APC/C component loss, and the protein functionally complements a yeast cdc26Δ mutant. RNAi phenotypic profiling in C. elegans embryos; functional complementation in yeast cdc26Δ BMC developmental biology Medium 17374146
2006 Loss of Cdc26 in zebrafish results in mitotic arrest followed by apoptosis in dividing cells, and improper re-entry into the cell cycle in quiescent/differentiated cells, demonstrating dual functions of the APC/C (including the Cdc26 subunit) in both dividing and post-mitotic cells in a vertebrate. Zebrafish genetic mutant analysis; live imaging; cell cycle marker analysis Developmental biology Medium 17141209
2019 In Arabidopsis, AtCDC26 (encoded by an upstream ORF of the AtTTM3 locus) is part of the plant APC/C, regulates accumulation of APC/C target proteins, and controls cell division, growth, and embryo development. Loss-of-function phenotyping; protein interaction assays showing APC/C membership; target protein accumulation assays Nature plants Medium 30737513
2021 CDC26 protein levels are severely decreased in aged human oocytes; knockdown of CDC26 in mouse oocytes causes aneuploidy and maturation defects, and overexpression of CDC26 partially rescues aging-associated oocyte defects, establishing CDC26 as a functional component required for proper meiotic progression in oocytes. Single-cell RNA-seq; immunocytochemistry; lentiviral overexpression in human oocytes; mouse oocyte knockdown Human reproduction Medium 34590680
2025 CDC26 promotes ferroptosis in human pancreatic ductal adenocarcinoma cells by facilitating ubiquitin-mediated proteasomal degradation of SLC7A11 (a key ferroptosis inhibitor) and by indirectly inhibiting the cell cycle, thereby sensitizing cells to ferroptosis. CDC26 overexpression/knockdown; ROS and lipid peroxidation assays; ubiquitination assay for SLC7A11; cell proliferation and invasion assays Clinical and experimental medicine Medium 41249642

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Identification of subunits of the anaphase-promoting complex of Saccharomyces cerevisiae. Science (New York, N.Y.) 240 8895471
2000 The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex. Proceedings of the National Academy of Sciences of the United States of America 156 10922056
1999 Budding yeast Bub2 is localized at spindle pole bodies and activates the mitotic checkpoint via a different pathway from Mad2. The Journal of cell biology 150 10352016
1999 Caveolin interacts with Trk A and p75(NTR) and regulates neurotrophin signaling pathways. The Journal of biological chemistry 137 9867838
1997 Distinct subunit functions and cell cycle regulated phosphorylation of 20S APC/cyclosome required for anaphase in fission yeast. Journal of cell science 114 9264466
1997 A novel yeast screen for mitotic arrest mutants identifies DOC1, a new gene involved in cyclin proteolysis. Molecular biology of the cell 79 9348530
2010 The APC/C subunit Cdc16/Cut9 is a contiguous tetratricopeptide repeat superhelix with a homo-dimer interface similar to Cdc27. The EMBO journal 63 20924356
2009 Insights into anaphase promoting complex TPR subdomain assembly from a CDC26-APC6 structure. Nature structural & molecular biology 45 19668213
2014 Structure of an APC3-APC16 complex: insights into assembly of the anaphase-promoting complex/cyclosome. Journal of molecular biology 31 25490258
2013 The Arabidopsis anaphase-promoting complex/cyclosome subunit 1 is critical for both female gametogenesis and embryogenesis(F). Journal of integrative plant biology 29 23206231
1992 Ty element-induced temperature-sensitive mutations of Saccharomyces cerevisiae. Genetics 27 1325386
2019 Concerted expression of a cell cycle regulator and a metabolic enzyme from a bicistronic transcript in plants. Nature plants 26 30737513
2006 The anaphase-promoting complex is required in both dividing and quiescent cells during zebrafish development. Developmental biology 24 17141209
1992 The CDC26 gene of Saccharomyces cerevisiae is required for cell growth only at high temperature. Molecular & general genetics : MGG 14 1736102
2015 LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C. PloS one 12 25723520
2007 Identification of the C. elegans anaphase promoting complex subunit Cdc26 by phenotypic profiling and functional rescue in yeast. BMC developmental biology 12 17374146
2021 miR-6769b-5p targets CCND-1 to regulate proliferation in cadmium-treated placental trophoblasts: Association with the impairment of fetal growth. Ecotoxicology and environmental safety 11 34953275
2021 CDC26 is a key factor in human oocyte aging. Human reproduction (Oxford, England) 8 34590680
2020 Drug combinations as effective anti-leishmanials against drug resistant Leishmania mexicana. RSC medicinal chemistry 8 33479685
2023 Identification of a circRNA-miRNA-mRNA network to explore the effects of circRNAs on Holstein bull testis after sexual maturity. Animal reproduction science 4 39492239
2022 Oncogenic Roles of Polycomb Repressive Complex 2 in Bladder Cancer and Upper Tract Urothelial Carcinoma. Biomedicines 4 36428492
1996 Fifteen open reading frames in a 30.8 kb region of the right arm of chromosome VI from Saccharomyces cerevisiae. Yeast (Chichester, England) 3 8686381
2024 Atypical cadherin, Fat2, regulates axon terminal organization in the developing Drosophila olfactory receptor neurons. iScience 2 39055932
2024 Homozygous missense variations of APC12 cause meiotic metaphase I arrest in oocytes and female infertility. American journal of obstetrics and gynecology 2 39542389
2025 Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma. International journal of molecular sciences 1 39859203
2025 CDC26 facilitates ferroptosis through SLC7A11 degradation and cell cycle arrest. Clinical and experimental medicine 1 41249642
2026 Biallelic mutations in ANAPC13 cause female infertility characterized by oocyte maturation arrest both in humans and mice. American journal of obstetrics and gynecology 0 41997520