Affinage

SKP1

S-phase kinase-associated protein 1 · UniProt P63208

Length
163 aa
Mass
18.7 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SKP1 is a conserved adaptor protein that forms the core bridge of SCF (SKP1–Cullin1–F-box) E3 ubiquitin ligases, linking diverse F-box substrate-recognition proteins to the cullin scaffold to direct substrate ubiquitination and proteasomal degradation (PMID:8706131, PMID:9499404). SKP1 binds F-box proteins through their F-box motif via a bipartite interface that engages both the F-box motif and the substrate-recognition domain, and it tethers them to Cullin1/Cdc53, which simultaneously positions the Rbx1 RING and E2 enzyme over the substrate held more than 100 Å away (PMID:8706131, PMID:11099048, PMID:11961546). Through this modular architecture, SCF complexes built on distinct F-box receptors target specific substrates — Skp2-SCF degrades p21 and p27, SCF(β-TrCP) degrades phospho-IκBα and β-catenin, and SCF activity controls Cyclin E1 turnover (PMID:9736735, PMID:10321728, PMID:10066435, PMID:33731859, PMID:32106628); the modularity is so general that engineered bifunctional molecules and covalent SKP1-targeting PROTACs can redirect SCF to degrade neo-substrates (PMID:11438690, PMID:38305738). Beyond catalysis, SKP1 acts as a chaperone that stabilizes F-box protein conformation and prevents their aggregation (PMID:21640084), and SCF assembly is itself regulated — F-box subcomplex formation suppresses CSN-mediated deneddylation of Cul1, and substrate binding can promote complex assembly (PMID:22767593, PMID:24085301). SKP1 also carries out SCF-independent roles in chromosome biology: it is required for chromosome segregation and genome stability (PMID:12417738), it controls CENP-E turnover at the midbody to permit cytokinesis (PMID:16682006), and it acts as an intrinsic metaphase-competence factor during meiotic prophase I, localizing to synapsed chromosome axes, evicting HORMAD proteins, and enabling the prophase-I-to-metaphase-I transition (PMID:32232159). In Dictyostelium, SKP1 is hydroxylated at Pro143 by an O2-dependent prolyl 4-hydroxylase and further modified by a cytoplasmic pentasaccharide, a modification that reshapes the F-box-binding interface and tunes SCF complex assembly, providing an oxygen-sensing input to ubiquitin ligase activity (PMID:9660787, PMID:15705570, PMID:24506136, PMID:28928219).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 High

    Established SKP1 as the adaptor that connects F-box substrate receptors to the ubiquitin-proteolysis machinery, defining its central function.

    Evidence Yeast genetics, Co-IP, two-hybrid, and in vivo ubiquitination assays identifying F-box binding and requirement for proteolysis of Sic1/Clb5/Cin2

    PMID:8706131

    Open questions at the time
    • Did not resolve the structural basis of F-box binding
    • Cullin connection not yet defined
  2. 1996 High

    Revealed an SCF-independent role by showing SKP1 is an intrinsic CBF3 kinetochore subunit, separating its mitotic from its cell-cycle functions genetically.

    Evidence Dosage suppressor screen, biochemical fractionation, centromere DNA binding, and ts-mutant phenotyping in budding yeast

    PMID:8706132

    Open questions at the time
    • Mechanism distinguishing kinetochore from proteolytic roles unresolved
    • Conservation of kinetochore role to metazoa not addressed
  3. 1998 High

    Defined the trimeric SCF architecture in both yeast and human cells, showing SKP1 bridges cullin to multiple F-box proteins with substrate specificity, and identified mammalian SCF targets.

    Evidence Reciprocal Co-IP, yeast complementation, antisense knockdown, and in vitro ubiquitination across yeast and human systems

    PMID:9499404 PMID:9636170 PMID:9736735

    Open questions at the time
    • Substrate phosphodegron recognition not yet mapped
    • Catalytic geometry of the complex unknown
  4. 1999 High

    Mapped SCF(β-TrCP) as the ligase for phospho-IκBα and β-catenin and delineated the SKP1 region and substrate residues required for recognition and ubiquitination.

    Evidence Co-IP, dominant-negative expression, deletion/point mutagenesis, and in vitro ubiquitination reconstitution

    PMID:10023660 PMID:10066435 PMID:10321728 PMID:10514433

    Open questions at the time
    • Atomic-resolution interface still lacking
    • Regulation of substrate phosphorylation upstream not addressed
  5. 2000 High

    Provided the atomic basis for how SKP1 grips F-box proteins, showing a bipartite interface that positions the substrate receptor for ubiquitination.

    Evidence X-ray crystallography of the Skp1–Skp2 complex

    PMID:11099048

    Open questions at the time
    • Did not capture the full cullin-RING assembly
    • Dynamics of substrate handoff not visualized
  6. 2001 High

    Demonstrated SCF modularity and revealed SKP1 participates in non-SCF complexes, broadening its functional repertoire.

    Evidence Chimeric Protac-1 in vitro/cell ubiquitination assays and affinity-purification/MS identification of the RAVE complex

    PMID:11283612 PMID:11438690

    Open questions at the time
    • Generality of non-SCF complexes in metazoa unclear
    • Functional importance of RAVE outside yeast not established
  7. 2002 High

    Resolved the elongated rigid SCF scaffold geometry and showed SKP1 contributes to genome stability in vivo, formally linking it to chromosome segregation.

    Evidence Full SCF crystal structure with structure-guided mutagenesis, plus transgenic-mouse double-transgenic rescue with cellular phenotyping

    PMID:11961546 PMID:12417738 PMID:12481031

    Open questions at the time
    • Whether segregation defects are SCF-dependent or SCF-independent not fully separated
    • CUL7-specific substrates not defined
  8. 2014 High

    Established that SKP1 post-translational modification in Dictyostelium tunes F-box binding, defining an oxygen-sensing layer of SCF regulation.

    Evidence MS glycan elucidation, recombinant prolyl-hydroxylase assays, gene disruption, and biophysics (CD/SAXS) with F-box binding assays

    PMID:15705570 PMID:24506136 PMID:25341530 PMID:9660787

    Open questions at the time
    • Whether equivalent modification operates in metazoan SKP1 unknown
    • Physiological O2 thresholds in vivo not quantified
  9. 2017 High

    Provided a structural mechanism for how glycosylation reshapes the F-box interface, explaining prior functional modulation data.

    Evidence NMR spectroscopy and molecular dynamics simulations of Dictyostelium Skp1

    PMID:28928219

    Open questions at the time
    • Direct link to in vivo SCF flux not established
    • Generalizability beyond Dictyostelium unaddressed
  10. 2012 High

    Showed SKP1-F-box subcomplex assembly and substrate binding feed back on SCF activation by regulating deneddylation and complex formation.

    Evidence Kinetic deneddylation assays and Co-IP/in vitro reconstitution with Fbxl3/Cry1

    PMID:22767593 PMID:24085301

    Open questions at the time
    • Identity of the cellular inhibitor blocking Fbxl3 assembly unknown
    • Quantitative contribution to substrate turnover in vivo unclear
  11. 2020 High

    Defined SKP1 as an intrinsic meiotic metaphase-competence factor acting at chromosome axes, extending its chromosome roles to meiosis.

    Evidence Conditional Skp1 knockout mice with immunofluorescence, CDK1 activity assay, and okadaic acid rescue; siRNA/CRISPR linking SKP1 to Cyclin E1 and chromosome instability

    PMID:32106628 PMID:32232159 PMID:33731859

    Open questions at the time
    • Whether axis localization requires SCF activity not resolved
    • Direct ubiquitination targets at the axis unidentified
  12. 2024 High

    Demonstrated SKP1 can be repurposed as a structural synaptonemal-complex building block and as a covalent PROTAC anchor, illustrating both moonlighting biology and chemical exploitation.

    Evidence C. elegans genetics with in vitro SC reconstitution and super-resolution microscopy; covalent chemoproteomics with SKP1-anchored PROTACs and genetic controls

    PMID:38305738 PMID:38354250

    Open questions at the time
    • Whether human SKP1 has an analogous SC structural role unknown
    • In vivo therapeutic window of SKP1 PROTACs untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SKP1's SCF-dependent and SCF-independent (kinetochore, midbody, meiotic axis) functions are mechanistically partitioned, and whether metazoan SKP1 is regulated by modification, remains unresolved.
  • No unified model separating adaptor versus structural roles
  • Modification-based regulation of metazoan SKP1 uncharacterized
  • Direct substrates at chromosome structures undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0005198 structural molecule activity 2 GO:0044183 protein folding chaperone 1
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2 GO:0000228 nuclear chromosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1474165 Reproduction 2 R-HSA-162582 Signal Transduction 2
Partners
BTRCCENPECUL1CUL7FBXL3FBXW7RBX1SKP2
Complex memberships
CBF3 kinetochore complexRAVE complexSCF (SKP1-Cullin1-F-box) E3 ligasesynaptonemal complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 SKP1 directly binds F-box proteins (Skp2, cyclin F, Cdc4p) through the F-box motif, and indirectly associates with cyclin A/Cdk2 through Skp2p. SKP1 is required for ubiquitin-mediated proteolysis of Cin2p, Clb5p, and the Cdk inhibitor Sic1p, establishing it as a core adaptor linking F-box substrate receptors to the ubiquitin proteolysis machinery. Yeast genetics (suppressor of cdc4 mutants), co-immunoprecipitation, two-hybrid, in vivo ubiquitination assays Cell High 8706131
1996 Budding yeast Skp1 is an intrinsic subunit of the CBF3 kinetochore complex that binds centromere DNA in vitro. Temperature-sensitive skp1 mutations cause two distinct arrest phenotypes: skp1-4 arrests in G2 with a short spindle (consistent with kinetochore defect), while skp1-3 arrests in G1, indicating distinct roles in kinetochore function and G1/S progression. Dosage suppressor screen, biochemical fractionation, centromere DNA-binding assay in vitro, temperature-sensitive mutant phenotyping Cell High 8706132
1998 Human CUL-1 forms a trimeric complex with SKP1 and SKP2 (the SCF complex) in human cells. Antisense depletion of SKP1, SKP2, or CUL-1 causes selective accumulation of p21(CIP1/WAF1) and cyclin D proteins, identifying these as in vivo SCF targets. Co-immunoprecipitation, antisense oligodeoxynucleotide knockdown with Western blot readout Proceedings of the National Academy of Sciences of the United States of America Medium 9736735
1998 In budding yeast, Skp1 bridges Cdc53 (cullin) to three F-box proteins (Cdc4, Met30, Grr1) and Skp1 interacts with Cdc53 in vivo. Cdc53 contains independent binding sites for Cdc34 (E2) and Skp1, acting as a scaffold. Different F-box proteins show functional specificity: Cdc4 degrades Sic1, Grr1 degrades Cln2, Met30 represses methionine biosynthesis genes, while the Cdc34-Cdc53-Skp1 core is required for all three. Co-immunoprecipitation in vivo, genetic analysis of F-box protein-specific functions Genes & development High 9499404
1998 Human CUL1 directly interacts with hSKP1 and the F-box protein SKP2 in vitro to form an SCF-like particle. hCUL1 complements yeast cdc53(ts) mutants, associates with ubiquitination-promoting activity in human cell extracts, and assembles into functional chimeric ubiquitin ligase complexes with yeast SCF components. Yeast two-hybrid, in vitro binding assay, yeast complementation, ubiquitination activity assay in cell extracts Proceedings of the National Academy of Sciences of the United States of America High 9636170
1999 The F-box protein beta-Trcp associates with Skp1 and Cul1 to form an SCF complex that interacts with beta-catenin in vivo. A dominant-negative beta-Trcp stabilizes beta-catenin, identifying SCF(beta-Trcp) as the ubiquitin ligase mediating beta-catenin degradation. Co-immunoprecipitation, dominant-negative overexpression with Western blot Oncogene Medium 10023660
1999 The SCF complex containing Skp1, Cul1, and F-box/WD40 protein HOS (FWD1 mouse homologue) specifically binds phosphorylated IkappaBalpha and beta-catenin. IkappaBalpha-E3 (containing Skp1, cullin-1, betaTrCP1 and betaTrCP2) catalyzes in vitro ubiquitination of phospho-IkappaBalpha in the presence of E1 and E2 enzymes. Co-immunoprecipitation, in vitro ubiquitination assay, dominant-negative mutant expression Oncogene / Biochemical and biophysical research communications High 10066435 10321728
1999 Residues 61-143 of Skp1 are required for binding to the F-box protein FWD1. Within the FWD1 F-box domain, Pro149, Ile160, and Leu164 are dispensable for Skp1 binding. In IkappaBalpha, an acidic residue at position 31 (in addition to phosphorylation at Ser32/Ser36) is required for FWD1-mediated ubiquitination. Deletion and point mutagenesis, co-immunoprecipitation, in vitro ubiquitination assay The Journal of biological chemistry High 10514433
2000 Crystal structure of human Skp2 bound to Skp1 reveals that Skp1 recruits F-box proteins through a bipartite interface involving both the F-box motif and the substrate-recognition domain of the F-box protein. The structure shows how Skp1 positions the F-box protein for substrate ubiquitination. X-ray crystallography Nature High 11099048
2001 Skp1 forms multiple protein complexes in budding yeast beyond SCF, including RAVE (regulator of V-ATPase), which contains Skp1, Rav1, and Rav2. RAVE associates with the V1 domain of vacuolar H+-ATPase and promotes glucose-triggered assembly of the V-ATPase holoenzyme. Sequential affinity purification with mass spectrometry, biochemical reconstitution Nature cell biology High 11283612
2001 Skp1/Skp2 complexes can be artificially redirected to ubiquitinate and degrade non-native substrate MetAP-2 when a bifunctional chimeric molecule (Protac-1) tethers the substrate to the SCF(beta-TRCP) complex via the IkappaBalpha phosphopeptide recognized by beta-TRCP F-box protein, demonstrating the modular substrate-recognition mechanism of SCF. In vitro ubiquitination assay with chimeric molecule, cell-based degradation assay Proceedings of the National Academy of Sciences of the United States of America High 11438690
2002 Crystal structure of the full Cul1-Rbx1-Skp1-F-box(Skp2) SCF complex shows Cul1 as an elongated rigid scaffold connecting Skp1-Fbox(Skp2) substrate recognition complex at its tip to Rbx1 at its globular domain, with the two functional ends held >100 Å apart. Mutations designed to reduce scaffold rigidity impair ubiquitination activity. X-ray crystallography, structure-guided mutagenesis, ubiquitination activity assay Nature High 11961546
1998 The cytoplasmic F-box binding protein SKP1 in Dictyostelium is modified post-translationally by a novel linear pentasaccharide (Galα1→6Galα1→Fucα1→2Galβ1→3GlcNAc) linked to hydroxyproline at Pro-143, representing an unusual cytoplasmic O-glycosylation. Mass spectrometry (quadrupole TOF), tandem MS, Edman degradation, GC-MS, exoglycosidase digestion The Journal of biological chemistry High 9660787
2002 CUL7 assembles a novel SCF-like E3 ubiquitin ligase complex containing Skp1, CUL7, the Fbx29 F-box protein, and ROC1. Unlike CUL1 which binds Skp1 alone, CUL7 interacts with the Skp1-Fbx29 complex but not Skp1 alone, and shows selectivity for Fbx29 but not betaTRCP2 or Skp2. Mass spectrometry (TAP), co-immunoprecipitation, in vitro binding assay Proceedings of the National Academy of Sciences of the United States of America Medium 12481031
1999 Skp2 inhibits cyclin A-Cdk2 kinase activity in vitro, both by direct inhibition of the complex and by inhibiting CDK-activating kinase phosphorylation of Cdk2. The F-box of Skp2 is required for binding to Skp1, while both N- and C-terminal regions of Skp2 mediate binding to cyclin A-Cdk2. Skp2 and p21(Cip1) bind cyclin A-Cdk2 in a mutually exclusive manner. In vitro kinase assay, co-immunoprecipitation, mutagenesis, overexpression cell cycle analysis Molecular and cellular biology Medium 9858587
2002 In vivo interference with Skp1 function (by a dominant-negative Cul1-N252 mutant that sequesters Skp1) causes multinucleated cells, centrosome and mitotic spindle abnormalities, and impaired chromosome segregation. These phenotypes are rescued in double transgenic mice expressing both Cul1-N252 and wild-type Skp1, establishing a causal role for Skp1 in chromosomal segregation and genome stability. Transgenic mouse model, genetic epistasis (double transgenic rescue), cell biology (centrosome/spindle imaging) Molecular and cellular biology High 12417738
2005 In Dictyostelium, Skp1 is hydroxylated at Pro143 by a cytoplasmic prolyl 4-hydroxylase (P4H1/PhyA) related to animal HIF-alpha class P4Hs. The enzyme requires O2, alpha-ketoglutarate, and ascorbate, is inhibited by CoCl2 and competitive substrates. Disruption of phyA blocks hydroxyproline-dependent glycosylation of Skp1 in vivo. Bioinformatics, gene disruption by homologous recombination, recombinant enzyme expression in E. coli, in vitro enzyme assay with [3H]GlcNAc transfer as readout, SDS-PAGE molecular weight shift The Journal of biological chemistry High 15705570
2006 SKP1 interacts with CENP-E at the midbody via CENP-E's coiled-coil domain (residues 955-1571) and the C-terminal 33 amino acids of Skp1. siRNA-mediated suppression of Skp1 in mitotic HeLa cells results in accumulation of telophase cells with elongated inter-cell bridges and CENP-E accumulation, indicating that Skp1-mediated CENP-E degradation at the midbody is essential for cytokinesis. Yeast two-hybrid, co-immunoprecipitation, in vitro binding, siRNA knockdown with immunocytochemistry, overexpression of truncation mutant Biochemical and biophysical research communications Medium 16682006
2011 Skp1 assists in correct folding of F-box proteins (Fbs2, Fbg3, Fbg4, Fbg5): co-expression of Skp1 with these F-box proteins enables their binding to N-glycoprotein substrates and prevents aggregate formation, increasing F-box protein cellular concentrations. Skp1 thus stabilizes the conformation of F-box proteins. Co-expression with co-immunoprecipitation, glycoprotein binding assay (ConA), aggregation analysis Biochemical and biophysical research communications Medium 21640084
2012 Assembly of the Skp1-F-box subcomplex with an F-box protein markedly inhibits CSN-mediated deneddylation of Cul1, with Fbw7-Skp1 inhibiting ~5-fold and Skp2-Cks1-Skp1 ~15%. Substrate addition further inhibits deneddylation ~2.5-fold. CSN can remain stably bound to deneddylated CRL and suppress its ubiquitin ligase activity by a non-catalytic mechanism. Kinetic enzyme assay (in vitro deneddylation), substrate addition experiments, quantitative biochemistry The Journal of biological chemistry High 22767593
2013 Substrate binding promotes formation of the SCF(Fbxl3) complex in vivo: Fbxl3 does not substantially associate with Skp1 and Cul1 unless its substrate Cry1 is co-expressed. An Fbxl3 mutant unable to bind Cry1 fails to form an SCF complex. In vitro, recombinant Fbxl3 associates with Skp1 and Cul1 without Cry1, suggesting an unknown inhibitory protein blocks complex formation in cells. Co-immunoprecipitation in mammalian cells, domain-swap analysis, in vitro reconstitution with recombinant proteins The Journal of biological chemistry Medium 24085301
2014 Glycosylation of Dictyostelium Skp1 at HyPro143 increases alpha-helical content, decreases beta-sheet content, and promotes a more compact and extended dimer conformation. Fully glycosylated Skp1 shows preferential binding to the mammalian F-box protein Fbs1 compared to unmodified Skp1, indicating glycosylation modulates F-box protein binding. Circular dichroism, small-angle X-ray scattering, analytical gel filtration, chemical cross-linking, in vitro F-box binding assay with purified recombinant proteins Biochemistry High 24506136
2014 In Dictyostelium, cells competent for full Skp1 glycosylation show greater abundance of SCF complexes containing CulE/FbxD and CulA/FbxA relative to cells defective in Skp1 hydroxylation or glycosylation. The CulE interactome includes higher levels of proteasomal regulatory particles in glycosylation-competent cells, suggesting increased SCF activity. Proteomic analysis of co-immunoprecipitates from wild-type vs. glycosylation mutants, mass spectrometry Molecular & cellular proteomics Medium 25341530
2017 NMR and molecular dynamics simulations of Dictyostelium Skp1 show that the pentasaccharide glycan interacts with the loop connecting two alpha-helices of the F-box-combining site, causing the helices to separate and creating a more accessible, dynamic F-box interface. This mechanism explains how glycosylation enhances F-box protein interactions. NMR spectroscopy, molecular dynamics simulation, mass spectrometry for glycan structure The Journal of biological chemistry High 28928219
2020 SKP1 localizes to synapsed chromosome axes during meiotic prophase I in spermatocytes and is required for the PI/MI transition. SKP1-deficient spermatocytes show premature desynapsis, loss of PLK1 and BUB1 at centromeres, persistence of HORMAD, γH2AX, RPA2, and MLH1 in diplonema, sharply reduced MPF (CDK1) activity, and failure to enter meiosis I even after okadaic acid treatment. SKP1 also evicts HORMAD proteins from synapsed chromosome axes. Conditional Skp1 knockout mice, immunofluorescence localization, okadaic acid rescue experiment, CDK1 activity assay Science advances High 32232159
2009 SKP1A silencing in dopaminergic neurons (SN4741 cells) causes delayed cell cycle completion, inability to arrest at G0/G1 upon differentiation, and formation of aggresome-like aggregates containing alpha-synuclein, ubiquitin, and proteasome subunits. Enforced SKP1A expression increases cell survival under proteasomal inhibition, suggesting a structural/protective role in dopaminergic neurons beyond E3 ligase activity. shRNA lentiviral knockdown, overexpression, cell cycle analysis, immunofluorescence for aggresome markers The Journal of biological chemistry Medium 19748892
2010 Human Hsp90-Sgt1 interacts with the Mis12 kinetochore complex. Co-inhibition of Sgt1 and the SCF subunit Skp1 increases Mis12 complex levels at kinetochores and restores timely chromosome alignment (relative to Sgt1 inhibition alone), but forms less-robust microtubule-binding sites, supporting a role for Skp1 in Mis12 complex turnover at kinetochores. Co-immunoprecipitation, siRNA double knockdown, kinetochore imaging, chromosome alignment assays The Journal of cell biology Medium 20404110
2015 Small molecule 6-O-angeloylplenolin (6-OAP) binds directly to Skp1 at sites critical for Skp1-Skp2 interaction (and Skp1-beta-TRCP interaction), leading to dissociation of Skp2-SCF and beta-TRCP-SCF E3 ligases and accumulation of their substrates p27, E-cadherin, and Cyclin B1. Skp1 overexpression attenuates and Skp1 knockdown enhances these effects. Biotin-compound pulldown, mass spectrometry, co-immunoprecipitation, Skp1 KD/OE validation, in vivo xenograft models Oncotarget Medium 26474281
2021 siRNA-mediated silencing of SKP1 (or CUL1) in fallopian tube secretory epithelial cells causes aberrant increases in Cyclin E1 protein levels and induces chromosome instability (CIN)-associated phenotypes including replication stress, DNA double-strand breaks, and chromothriptic events, mechanistically linking SKP1 to Cyclin E1 turnover and chromosome stability. siRNA knockdown, CRISPR/Cas9 deletion, quantitative imaging microscopy, Western blot for Cyclin E1 British journal of cancer / Cancers Medium 32106628 33731859
2024 A cysteine-reactive covalent recruiter (EN884) targeting SKP1 can be incorporated into PROTACs to degrade neo-substrate proteins (BRD4, androgen receptor) in a SKP1- and proteasome-dependent manner, demonstrating that the SKP1 adaptor protein within the SCF complex can serve as a direct PROTAC anchor for targeted protein degradation. Covalent chemoproteomic target identification, PROTAC synthesis, SKP1 siRNA knockdown, proteasome inhibition, Western blot ACS chemical biology Medium 38305738
2024 In C. elegans, two paralogous Skp1-related proteins (SKR-1 and SKR-2) serve as structural components of the synaptonemal complex (SC), repurposing their SCF-forming interfaces to dimerize and interact with meiosis-specific SC proteins, driving meiotic synapsis independently of SCF ubiquitin ligase activity. SKR-1 enables formation of a soluble complex with SC proteins in vitro, proposed to represent a complete SC building block. Genetic analysis (RNAi/mutants), in vitro reconstitution of SC building block, co-immunoprecipitation, super-resolution microscopy Science advances High 38354250

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Proceedings of the National Academy of Sciences of the United States of America 1912 11438690
2002 Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 1246 11961546
1996 SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 1188 8706131
2000 Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex. Nature 512 11099048
1999 The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin. Oncogene 396 10023660
1998 Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins. Proceedings of the National Academy of Sciences of the United States of America 377 9736735
2007 Patterns of gene duplication in the plant SKP1 gene family in angiosperms: evidence for multiple mechanisms of rapid gene birth. The Plant journal : for cell and molecular biology 320 17470057
1996 Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression. Cell 251 8706132
1998 Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box proteincomplexes that regulate cell division and methionine biosynthesis in yeast. Genes & development 242 9499404
2001 Skp1 forms multiple protein complexes, including RAVE, a regulator of V-ATPase assembly. Nature cell biology 231 11283612
2011 Stability of plant immune-receptor resistance proteins is controlled by SKP1-CULLIN1-F-box (SCF)-mediated protein degradation. Proceedings of the National Academy of Sciences of the United States of America 202 21873230
2001 SKP1-SnRK protein kinase interactions mediate proteasomal binding of a plant SCF ubiquitin ligase. The EMBO journal 190 11387208
1999 HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-catenin. Oncogene 164 10321728
2002 CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex. Proceedings of the National Academy of Sciences of the United States of America 136 12481031
1998 Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein. Proceedings of the National Academy of Sciences of the United States of America 119 9636170
2011 Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP, sequentially regulate glycolysis during the cell cycle. Proceedings of the National Academy of Sciences of the United States of America 116 21402913
2012 Deconjugation of Nedd8 from Cul1 is directly regulated by Skp1-F-box and substrate, and the COP9 signalosome inhibits deneddylated SCF by a noncatalytic mechanism. The Journal of biological chemistry 109 22767593
2004 p27(Kip1) stabilization and G(1) arrest by 1,25-dihydroxyvitamin D(3) in ovarian cancer cells mediated through down-regulation of cyclin E/cyclin-dependent kinase 2 and Skp1-Cullin-F-box protein/Skp2 ubiquitin ligase. The Journal of biological chemistry 109 15075339
2002 The Caenorhabditis elegans Skp1-related gene family: diverse functions in cell proliferation, morphogenesis, and meiosis. Current biology : CB 106 11864567
1999 IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2. Biochemical and biophysical research communications 105 10066435
2001 Interaction of the virulence protein VirF of Agrobacterium tumefaciens with plant homologs of the yeast Skp1 protein. Current biology : CB 97 11250154
1998 Two F-box/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes together with cullin-1 in the fission yeast SCF (Skp1-Cullin-1-F-box) ubiquitin ligase. Genes to cells : devoted to molecular & cellular mechanisms 93 9990507
2000 Clink, a nanovirus-encoded protein, binds both pRB and SKP1. Journal of virology 87 10708410
2015 Atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 controls the core epithelial-to-mesenchymal transition-inducing transcription factors. Oncotarget 80 25460509
2013 Genetically engineered mouse models for functional studies of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases. Cell research 79 23528706
1999 Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2. Molecular and cellular biology 76 9858587
2014 Skp1-Cullin-F-box (SCF)-type ubiquitin ligase FBXW7 negatively regulates spermatogonial stem cell self-renewal. Proceedings of the National Academy of Sciences of the United States of America 69 24879440
2010 The Skp1-like protein SSK1 is required for cross-pollen compatibility in S-RNase-based self-incompatibility. The Plant journal : for cell and molecular biology 67 20070569
2006 AhSSK1, a novel SKP1-like protein that interacts with the S-locus F-box protein SLF. The Plant journal : for cell and molecular biology 64 16709194
2016 Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase. PLoS pathogens 62 26837067
2002 Multiple Skp1-related proteins in Caenorhabditis elegans: diverse patterns of interaction with Cullins and F-box proteins. Current biology : CB 59 11864566
1998 The cytoplasmic F-box binding protein SKP1 contains a novel pentasaccharide linked to hydroxyproline in Dictyostelium. The Journal of biological chemistry 59 9660787
2011 The SKP1-Cul1-F-box and leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A) protein. The Journal of biological chemistry 56 21757720
2016 Lys29-linkage of ASK1 by Skp1-Cullin 1-Fbxo21 ubiquitin ligase complex is required for antiviral innate response. eLife 55 27063938
2003 Highly heterogeneous rates of evolution in the SKP1 gene family in plants and animals: functional and evolutionary implications. Molecular biology and evolution 55 14595103
2001 Phosphorylation- and Skp1-independent in vitro ubiquitination of E2F1 by multiple ROC-cullin ligases. Cancer research 54 11245432
2015 Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors. Oncotarget 53 26474281
2003 Preferential interaction of TIP120A with Cul1 that is not modified by NEDD8 and not associated with Skp1. Biochemical and biophysical research communications 53 12684064
2020 SKP1 drives the prophase I to metaphase I transition during male meiosis. Science advances 52 32232159
2010 Hsp90-Sgt1 and Skp1 target human Mis12 complexes to ensure efficient formation of kinetochore-microtubule binding sites. The Journal of cell biology 50 20404110
2007 Thiazolidinediones modulate the expression of beta-catenin and other cell-cycle regulatory proteins by targeting the F-box proteins of Skp1-Cul1-F-box protein E3 ubiquitin ligase independently of peroxisome proliferator-activated receptor gamma. Molecular pharmacology 49 17569795
2003 Eradication of pathogenic beta-catenin by Skp1/Cullin/F box ubiquitination machinery. Proceedings of the National Academy of Sciences of the United States of America 49 14563921
2005 The Skp1 prolyl hydroxylase from Dictyostelium is related to the hypoxia-inducible factor-alpha class of animal prolyl 4-hydroxylases. The Journal of biological chemistry 46 15705570
2013 TGBp3 triggers the unfolded protein response and SKP1-dependent programmed cell death. Molecular plant pathology 45 23458484
2012 Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity. Stem cells (Dayton, Ohio) 45 22553175
2002 In vivo interference with Skp1 function leads to genetic instability and neoplastic transformation. Molecular and cellular biology 45 12417738
2019 Interaction between Brassica yellows virus silencing suppressor P0 and plant SKP1 facilitates stability of P0 in vivo against degradation by proteasome and autophagy pathways. The New phytologist 44 30664234
1996 Schizosaccharomyces pombe skp1+ encodes a protein kinase related to mammalian glycogen synthase kinase 3 and complements a cdc14 cytokinesis mutant. Molecular and cellular biology 43 8524294
2013 Role of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases in skin cancer. Journal of genetics and genomics = Yi chuan xue bao 42 23522382
2012 Skp1-Cul1-F-box ubiquitin ligase (SCF(βTrCP))-mediated destruction of the ubiquitin-specific protease USP37 during G2-phase promotes mitotic entry. The Journal of biological chemistry 42 23027877
2009 A sporadic Parkinson disease model via silencing of the ubiquitin-proteasome/E3 ligase component SKP1A. The Journal of biological chemistry 42 19748892
2007 Cdc34 C-terminal tail phosphorylation regulates Skp1/cullin/F-box (SCF)-mediated ubiquitination and cell cycle progression. The Biochemical journal 42 17461777
2012 The Skp1 protein from Toxoplasma is modified by a cytoplasmic prolyl 4-hydroxylase associated with oxygen sensing in the social amoeba Dictyostelium. The Journal of biological chemistry 41 22648409
2021 Tomato chlorosis virus-encoded p22 suppresses auxin signalling to promote infection via interference with SKP1-Cullin-F-boxTIR1 complex assembly. Plant, cell & environment 40 34105183
2011 Drosophila homeodomain-interacting protein kinase inhibits the Skp1-Cul1-F-box E3 ligase complex to dually promote Wingless and Hedgehog signaling. Proceedings of the National Academy of Sciences of the United States of America 39 21628596
2009 The myxoma virus m-t5 ankyrin repeat host range protein is a novel adaptor that coordinately links the cellular signaling pathways mediated by Akt and Skp1 in virus-infected cells. Journal of virology 38 19776120
2015 The E3 Ubiquitin Ligase Adaptor Protein Skp1 Is Glycosylated by an Evolutionarily Conserved Pathway That Regulates Protist Growth and Development. The Journal of biological chemistry 37 26719340
1999 Molecular dissection of the interactions among IkappaBalpha, FWD1, and Skp1 required for ubiquitin-mediated proteolysis of IkappaBalpha. The Journal of biological chemistry 37 10514433
1996 Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2). Cytogenetics and cell genetics 37 8646875
2009 A cytoplasmic prolyl hydroxylation and glycosylation pathway modifies Skp1 and regulates O2-dependent development in Dictyostelium. Biochimica et biophysica acta 36 19914348
2003 Regulation of Ste7 ubiquitination by Ste11 phosphorylation and the Skp1-Cullin-F-box complex. The Journal of biological chemistry 36 12668671
2022 Brusatol has therapeutic efficacy in non-small cell lung cancer by targeting Skp1 to inhibit cancer growth and metastasis. Pharmacological research 35 34998973
2002 Complex glycosylation of Skp1 in Dictyostelium: implications for the modification of other eukaryotic cytoplasmic and nuclear proteins. Glycobiology 35 11886837
1980 Organ of Corti-specific polypeptides: OCP-I and OCP-II. Archives of oto-rhino-laryngology 35 7458746
2024 Skp1 proteins are structural components of the synaptonemal complex in C. elegans. Science advances 33 38354250
2004 Molecular interactions of fission yeast Skp1 and its role in the DNA damage checkpoint. Genes to cells : devoted to molecular & cellular mechanisms 33 15147268
2001 A non-Golgi alpha 1,2-fucosyltransferase that modifies Skp1 in the cytoplasm of Dictyostelium. The Journal of biological chemistry 33 11423539
2014 Pepper suppressor of the G2 allele of skp1 interacts with the receptor-like cytoplasmic kinase1 and type III effector AvrBsT and promotes the hypersensitive cell death response in a phosphorylation-dependent manner. Plant physiology 31 24686111
2024 Exploiting the Cullin E3 Ligase Adaptor Protein SKP1 for Targeted Protein Degradation. ACS chemical biology 30 38305738
2014 Glycosylation of Skp1 promotes formation of Skp1-cullin-1-F-box protein complexes in dictyostelium. Molecular & cellular proteomics : MCP 30 25341530
2012 Identification of a Skp1-like protein interacting with SFB, the pollen S determinant of the gametophytic self-incompatibility in Prunus. Plant physiology 30 22548785
2002 Molecular cloning and expression of a UDP-N-acetylglucosamine (GlcNAc):hydroxyproline polypeptide GlcNAc-transferase that modifies Skp1 in the cytoplasm of dictyostelium. The Journal of biological chemistry 30 12244115
2001 Analysis of Skp1 glycosylation and nuclear enrichment in Dictyostelium. Glycobiology 29 11358877
1999 Identification of a UDP-GlcNAc:Skp1-hydroxyproline GlcNAc-transferase in the cytoplasm of Dictyostelium. The Journal of biological chemistry 29 10593934
2018 A Structure-Based Strategy for Engineering Selective Ubiquitin Variant Inhibitors of Skp1-Cul1-F-Box Ubiquitin Ligases. Structure (London, England : 1993) 28 30033217
2016 Skp1: Implications in cancer and SCF-oriented anti-cancer drug discovery. Pharmacological research 28 27238229
2013 Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF(Fbxl3)) protein complex. The Journal of biological chemistry 28 24085301
2021 Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis. Cell biology and toxicology 27 33656636
2021 Reduced SKP1 and CUL1 expression underlies increases in Cyclin E1 and chromosome instability in cellular precursors of high-grade serous ovarian cancer. British journal of cancer 27 33731859
2017 Proteomic identification of the oncoprotein STAT3 as a target of a novel Skp1 inhibitor. Oncotarget 27 27835873
2012 Several components of SKP1/Cullin/F-box E3 ubiquitin ligase complex and associated factors play a role in Agrobacterium-mediated plant transformation. The New phytologist 27 22486382
2011 Skp1 stabilizes the conformation of F-box proteins. Biochemical and biophysical research communications 27 21640084
2006 Interaction of Skp1 with CENP-E at the midbody is essential for cytokinesis. Biochemical and biophysical research communications 27 16682006
2017 O2 sensing-associated glycosylation exposes the F-box-combining site of the Dictyostelium Skp1 subunit in E3 ubiquitin ligases. The Journal of biological chemistry 26 28928219
2020 Reduced SKP1 Expression Induces Chromosome Instability through Aberrant Cyclin E1 Protein Turnover. Cancers 25 32106628
2010 Prolyl hydroxylation- and glycosylation-dependent functions of Skp1 in O2-regulated development of Dictyostelium. Developmental biology 25 20969846
2014 Glycosylation of Skp1 affects its conformation and promotes binding to a model f-box protein. Biochemistry 24 24506136
2003 Skp1 and the F-box protein Pof6 are essential for cell separation in fission yeast. The Journal of biological chemistry 24 12511573
2000 sconC, a gene involved in the regulation of sulphur metabolism in Aspergillus nidulans, belongs to the SKP1 gene family. Molecular & general genetics : MGG 24 11085267
2025 Isoorientin Ameliorates Macrophage Pyroptosis and Atherogenesis by Reducing KDM4A Levels and Promoting SKP1-Cullin1-F-box E3 Ligase-mediated NLRP3 Ubiquitination. Inflammation 23 40133580
2023 Cullin-associated and neddylation-dissociated 1 regulate reprogramming of lipid metabolism through SKP1-Cullin-1-F-boxFBXO11 -mediated heterogeneous nuclear ribonucleoprotein A2/B1 ubiquitination and promote hepatocellular carcinoma. Clinical and translational medicine 23 37837399
2012 SKP1-like-related genes interact with various F-box proteins and may form SCF complexes with Cullin-F-box proteins in wheat. Molecular biology reports 23 23065282
2012 Structural, expression and interaction analysis of rice SKP1-like genes. DNA research : an international journal for rapid publication of reports on genes and genomes 23 23248203
2004 Mcs2 and a novel CAK subunit Pmh1 associate with Skp1 in fission yeast. Biochemical and biophysical research communications 23 15555586
2018 GmSK1, an SKP1 homologue in soybean, is involved in the tolerance to salt and drought. Plant physiology and biochemistry : PPB 22 29544210
2014 Ubiquitin-conjugating enzyme Cdc34 and ubiquitin ligase Skp1-cullin-F-box ligase (SCF) interact through multiple conformations. The Journal of biological chemistry 22 25425648
1998 Grr1 functions in the ubiquitin pathway in Saccharomyces cerevisiae through association with Skp1. Molecular & general genetics : MGG 22 9491072
2019 Inhibition of Skp1-Cullin-F-box complexes during bovine oocyte maturation and preimplantation development leads to delayed development of embryos†. Biology of reproduction 21 30535233
2018 The SKP1-Cullin-F-box E3 ligase βTrCP and CDK2 cooperate to control STIL abundance and centriole number. Open biology 21 29445034
2012 Role of the Skp1 prolyl-hydroxylation/glycosylation pathway in oxygen dependent submerged development of Dictyostelium. BMC developmental biology 21 23098648

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