| 1999 |
SGT1 (yeast ortholog) physically associates with Skp1p in vivo and in vitro, is a novel subunit of the SCF (Skp1p/Cdc53p/F-box protein) ubiquitin ligase complex, and is required for assembling the yeast kinetochore complex CBF3 via activation of Ctf13p. Human SGT1 rescues the yeast null mutation, demonstrating functional conservation. |
Dosage suppressor screen, in vivo and in vitro co-immunoprecipitation/pulldown, conditional mutant phenotypic analysis, in vitro ubiquitination assay, cross-species complementation |
Molecular cell |
High |
10445024
|
| 2002 |
Plant SGT1 orthologs interact with RAR1 and associate with SKP1 and CUL1 (SCF ubiquitin ligase subunits) as well as two COP9 signalosome components, linking disease resistance signaling to ubiquitination machinery. |
Yeast two-hybrid, co-immunoprecipitation, virus-induced gene silencing (VIGS) functional assay |
Science |
High |
11847307
|
| 2003 |
Human SGT1 binds HSP90 through its CS (CHORD-SGT1) domain, not through its tetratricopeptide repeat (TPR) domain, and this interaction does not require ATP (unlike p23-HSP90 binding). The CS domain adopts a beta-sandwich fold structurally similar to p23 but functionally distinct. |
NMR spectroscopy, 3D structure determination, binding assays with domain deletions |
The Journal of biological chemistry |
High |
14761955
|
| 2003 |
HSP90 interacts with SGT1 (via SGT1's TPR motif and p23-like domain) and with RAR1, forming a chaperone complex that is essential for R protein (RPS2, N)-mediated plant disease resistance; HSP90 inhibition abrogates resistance responses. |
Yeast two-hybrid, co-immunoprecipitation, pharmacological inhibition (geldanamycin), loss-of-function genetics |
Proceedings of the National Academy of Sciences of the United States of America |
High |
14504384 14583611
|
| 2004 |
Human Sgt1 depletion by RNAi in HeLa cells causes defective kinetochore assembly, preventing localization of Hec1, CENP-E, CENP-F, and CENP-I (but not CENP-C) to mitotic kinetochores, weakening the spindle checkpoint and causing chromosome alignment defects. |
RNA interference, immunofluorescence microscopy, mitotic checkpoint assay |
EMBO reports |
High |
15133482
|
| 2004 |
In budding yeast, Sgt1 interacts with Hsp90 (Hsc82) via its N-terminal TPR-containing region; Hsp90 binding to Sgt1 stimulates Sgt1-Skp1 interaction, and together Sgt1 and Hsp90 promote Skp1-Ctf13 binding to assemble the CBF3 kinetochore complex. |
Co-immunoprecipitation, genetic analysis of sgt1 mutants, in vitro binding assays |
Molecular and cellular biology |
High |
15340069
|
| 2007 |
Many mammalian NLR proteins (NALP3, IPAF, Nod2) interact with SGT1 and HSP90; siRNA knockdown of SGT1 abrogates inflammasome activity, and HSP90 inhibition blocks Nod2-mediated NF-κB activation and NALP3-mediated inflammation in mice. |
Co-immunoprecipitation, siRNA knockdown, in vivo mouse inflammation model, pharmacological inhibition |
Nature immunology |
High |
17435760
|
| 2007 |
SGT1 is required for Nod1 activation: siRNA depletion of SGT1 prevents multiple Nod1-dependent cellular responses without affecting Nod1 protein stability; HSP90 depletion destabilizes Nod1 protein. Rar1 ortholog Chp1 is not required for Nod1 function. |
siRNA knockdown, functional cellular assays, immunoblot |
Proceedings of the National Academy of Sciences of the United States of America |
High |
17420470
|
| 2007 |
Arabidopsis SGT1a and SGT1b associate with HSC70 chaperones in the cytosol and nucleus in vivo; the C-terminal SGS domain of SGT1b is required for HSC70 interaction and for nuclear accumulation of SGT1b. SGT1 functions as an HSC70 cofactor. |
Affinity purification-mass spectrometry, co-immunoprecipitation, subcellular fractionation, domain-deletion analysis, confocal microscopy |
The Plant cell |
High |
18065690
|
| 2007 |
NMR-based mapping of the plant SGT1 CS domain shows that RAR1 CHORD II and the HSP90 N-terminal domain interact on opposite faces of the CS domain. Mutagenesis confirms that the SGT1-HSP90 interaction is required for accumulation of the R protein Rx. RAR1 may enhance the SGT1-HSP90 interaction by promoting ternary complex formation. |
NMR surface mapping, random mutagenesis, biochemical reconstitution, in planta functional assay |
The Plant cell |
High |
18032631
|
| 2007 |
Tobacco SGT1 undergoes MAPK (SIPK)-mediated phosphorylation at a canonical MAPK motif; phospho-mimic and phospho-null mutations at this site alter SGT1 nuclear accumulation and impair N-mediated TMV resistance. SGT1 controls nucleocytoplasmic partitioning of the N resistance protein. |
Mass spectrometry, site-directed mutagenesis, confocal microscopy, pathogen resistance assay |
The New phytologist |
High |
23731343
|
| 2008 |
Crystal structure of the core Hsp90-Sgt1 complex reveals a distinct interaction site on the Hsp90 N-terminal domain. Interface mutations in Sgt1 that abrogate Hsp90 binding disrupt Sgt1-dependent functions in plants and yeast. Sgt1 bridges the Hsp90 chaperone system to SCF ubiquitin ligase complexes. |
X-ray crystallography, site-directed mutagenesis, in vivo functional assays in plants and yeast |
The EMBO journal |
High |
18818696
|
| 2008 |
NMR and mutational analysis of HSP90 define the binding surface for the SGT1 CS domain. Full-length SGT1 can displace p23 from HSP90, yet CS and p23 bind non-competitively to different HSP90 regions. RAR1 partly overlaps the CS-domain binding site on HSP90. A compensatory mutant pair between SGT1 and HSP90 that restores Rx-mediated virus resistance was identified. |
NMR spectroscopy, site-directed mutagenesis, in vivo virus resistance assay |
EMBO reports |
High |
18833289
|
| 2008 |
Drosophila Sgt1 stabilizes Polo kinase protein levels; loss of Sgt1 reduces total Polo protein, prevents centrosome maturation and pericentriolar material recruitment, and causes highly abnormal mitotic spindles. Overexpression of Polo substantially rescues the sgt1 centrosome defects. |
Drosophila genetic mutant analysis, immunofluorescence, rescue by Polo overexpression |
The EMBO journal |
High |
19131964
|
| 2008 |
Yeast Sgt1 forms homodimers via its N-terminal Skp1-binding domain (aa 1–211); dimerization is required for Sgt1-Skp1 binding and kinetochore assembly. Restoring dimerization of a dimerization-deficient mutant via a heterologous dimerization domain rescues kinetochore function. |
In vitro and in vivo co-immunoprecipitation, analytical ultracentrifugation, domain deletion, functional complementation |
The Journal of biological chemistry |
High |
19073600
|
| 2009 |
Protein kinase CK2 phosphorylates yeast Sgt1 at Ser361, and this phosphorylation inhibits Sgt1 dimerization. |
In vitro kinase assay, phospho-site mutagenesis, dimerization assay |
The Journal of biological chemistry |
High |
19398558
|
| 2010 |
Crystal structure of Hsp90-CS-CHORD ternary complex defines the architecture for recruiting NLR receptors; mutational and biochemical analyses show that CHORD and CS domains independently bind Hsp90 and can coexist in complexes, controlling the ATPase-dependent conformational cycle of the chaperone. |
X-ray crystallography, mutagenesis, biochemical binding assays |
Molecular cell |
High |
20670895
|
| 2010 |
Human Hsp90-Sgt1 interacts with the Mis12 kinetochore complex; inhibition of Hsp90 or Sgt1 destabilizes the Mis12 complex and delays chromosome alignment due to inefficient microtubule-binding site formation. Coinhibition of Sgt1 and Skp1 increases Mis12 at kinetochores, suggesting competitive regulation. |
Co-immunoprecipitation, RNAi knockdown, chromosome alignment and kinetochore localization assays |
The Journal of cell biology |
High |
20404110
|
| 2012 |
Plk1 phosphorylates Sgt1 at Ser331 at kinetochores during prometaphase; this phosphorylation enhances the association of the Hsp90-Sgt1 chaperone with the MIS12 complex to stabilize it at kinetochores and recruit the NDC80 complex, promoting stable microtubule attachment. Loss of this phosphorylation causes chromosome misalignment. |
In vitro kinase assay, phospho-site mutagenesis, co-immunoprecipitation, kinetochore localization assay, chromosome alignment analysis |
Molecular and cellular biology |
High |
22869522
|
| 2012 |
In Drosophila neuroblasts, Sgt1 acts through an LKB1/AMPK pathway to establish apical cortical polarity at prophase; activated AMPKα rescues the sgt1 cortical polarity defect. Sgt1 and Hsp90 (Hsp83) act in the same pathway upstream of LKB1-AMPK. |
Drosophila genetic screen, double-mutant epistasis, rescue by activated AMPKα |
Developmental biology |
Medium |
22248825
|
| 2012 |
Scrib (mammalian Scribble) associates with Sgt1 via its LRR domain; Sgt1 and HSP90 are required to maintain proper Scrib protein levels. Loss of Sgt1-HSP90 destabilizes Scrib and reduces the Scrib-βPix-PAK complex, blocking HGF-mediated epithelial morphogenesis. |
Co-immunoprecipitation, siRNA knockdown, 3D epithelial morphogenesis assay, immunoblot |
Journal of cell science |
Medium |
22623728
|
| 2013 |
The Salmonella effector SspH2 interacts with SGT1 specifically through SGT1's NLR co-chaperone function (not its cell-cycle function); SspH2 ubiquitinates Nod1, and SGT1 interaction enhances SspH2 in vitro ubiquitination activity and protein stability. Catalytically active SspH2 can induce Nod1 activity in an agonist-independent manner. |
Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, domain-specificity analysis |
PLoS pathogens |
High |
23935490
|
| 2013 |
Human SGT1 regulates Akt signaling in gastric cancer cells by promoting beta-TrCP-mediated degradation of PHLPP1 (the Akt Ser473 phosphatase); SGT1 enhances the PHLPP1-beta-TrCP interaction, reducing PHLPP1 levels and increasing Akt Ser473 phosphorylation. |
siRNA knockdown, co-immunoprecipitation, immunoblot for phosphorylation status, colony formation assay |
Molecular biology reports |
Medium |
23440515
|
| 2017 |
Crystal structure of the yeast Sgt1 TPR domain in complex with the Skp1 BTB/POZ domain at 2.8 Å reveals that Skp1 binds the concave surface of the Sgt1 TPR domain via conserved residues. Sgt1 dimerization in yeast occurs via a TPR insertion absent from monomeric human Sgt1. Skp1 binding is an essential function of Sgt1 in yeast. |
X-ray crystallography, mutagenesis, in vitro binding assay, yeast complementation |
Scientific reports |
High |
28139700
|
| 2017 |
The SGT1-HSP90 complex is required for CENP-A deposition at centromeres; SGT1-HSP90 promotes recognition of CENP-A by COPS8 (part of the CUL4A-RBX1-COPS8 E3 ligase), enabling CENP-A K124 ubiquitylation required for centromeric CENP-A deposition. |
siRNA knockdown, co-immunoprecipitation, chromatin immunoprecipitation, ubiquitylation assay |
Cell cycle |
Medium |
28816574
|
| 2017 |
PHLPP1 interacts with SGT1 and stabilizes it by dephosphorylating SGT1 at Ser-17, Ser-249, Ser-289, and Thr-233, preventing SGT1 association with the E3 ligase RNF41 and consequent ubiquitin-mediated SGT1 degradation. Loss of PHLPP1 causes SGT1 degradation and defective kinetochore assembly. |
Co-immunoprecipitation, in vitro dephosphorylation assay, ubiquitination assay, site-directed mutagenesis, kinetochore assembly assay |
The Journal of biological chemistry |
High |
28696259
|
| 2020 |
The bacterial effector RipAC associates with SGT1, inhibits its interaction with MAP kinases, and prevents MAPK-mediated phosphorylation of a canonical MAPK motif in the C-terminal domain of SGT1. This phosphorylation is enhanced upon immune activation and contributes to NLR (RPS2)-mediated immunity. |
Co-immunoprecipitation, in vitro kinase assay, phospho-site mutagenesis, bacterial pathogen resistance assay |
PLoS pathogens |
High |
32976518
|
| 2020 |
SUGT1 stabilizes microtubule plus-ends of host cells through modulation of microtubule acetylation and EB1 comet formation; this promotes HIV-1 retrograde trafficking and nuclear import of the viral genome, making SUGT1 a permissive factor for HIV-1 infection. |
siRNA knockdown, live-cell imaging, microtubule acetylation assay, EB1 comet analysis, HIV-1 infectivity assay |
Cell death and differentiation |
Medium |
32514048
|
| 2020 |
Necdin recruits the SGT1-HSP90 chaperone machinery to stabilize BMAL1, a core circadian clock component; depletion of necdin or SGT1/HSP90 leads to BMAL1 degradation via the ubiquitin-proteasome system and disrupts circadian rhythms. |
Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, cycloheximide chase, circadian reporter assay |
Nucleic acids research |
Medium |
32667666
|
| 2020 |
lncRNA SAM interacts with and stabilizes Sugt1 protein in proliferating myoblasts; loss of SAM or Sugt1 disrupts kinetochore assembly (mislocalization of Dsn1 and Hec1) and impairs myoblast proliferation and muscle regeneration. |
RNA-protein pulldown, co-immunoprecipitation, kinetochore localization assay, genetic deletion in mice |
Nature communications |
Medium |
32483152
|
| 2023 |
Sugt1 promotes ubiquitination of p21 via the E3 ligase Trim21; loss of Sugt1 in muscle stem cells causes p21 accumulation, G2/M cell cycle arrest, and cellular senescence, impairing muscle regeneration. |
Co-immunoprecipitation, ubiquitination assay, cell cycle analysis, in vivo genetic deletion |
Life medicine |
Medium |
39872547
|
| 2024 |
SGT1 interacts with NSL1 (a negative regulator of SA-mediated defense) and promotes SCF-dependent degradation of NSL1 to facilitate NLR immune activation; SIPK-mediated phosphorylation of SGT1 potentiates this NSL1 degradation. This SGT1-NSL1 module functions downstream of multiple NLRs. |
TurboID proximity labeling, co-immunoprecipitation, degradation assays, phospho-site mutagenesis, NLR resistance assay |
Molecular plant |
Medium |
39066482
|
| 2003 |
Sgt1 interacts with S100A6 (calcyclin) and other S100 proteins (S100B, S100P) in a calcium-regulated manner; the S100A6-binding domain maps to the 71 C-terminal residues of Sgt1. S100A6 binding inhibits casein kinase II-mediated phosphorylation of this domain and does not interfere with Skp1-Sgt1 binding. |
Affinity chromatography, chemical cross-linking, co-immunoprecipitation from cell extract, in vitro kinase assay |
The Journal of biological chemistry |
Medium |
12746458
|
| 2007 |
Sgt1 interacts with Hsp70 in addition to Hsp90; the C-terminal region of Sgt1 is required for both interactions. S100A6 overexpression decreases Hsp70 and Hsp90 binding to Sgt1 in a calcium-dependent manner. |
Co-immunoprecipitation, affinity chromatography, ELISA, deletion mutant analysis |
Biochemical and biophysical research communications |
Medium |
17466273
|
| 2010 |
S100A6 in its Ca2+-bound form mediates nuclear translocation of Sgt1 upon heat shock; dephosphorylation of Sgt1 at Ser299 (and Ser249) promotes nuclear translocation, likely through disruption of the Sgt1-Hsp90 complex, while non-phosphorylatable Sgt1 mutants show enhanced S100A6 interaction and reduced Hsp90 binding. |
siRNA knockdown of S100A6, phospho-mutant transfection, subcellular fractionation, co-immunoprecipitation |
Amino acids / The international journal of biochemistry & cell biology |
Medium |
20213445 21864708
|
| 2015 |
The D2 and D3 domains of eEF1A1 interact with the TPR domain of Sgt1; Sgt1 competes with viral RNA for binding to eEF1A1 in vitro. |
Co-immunoprecipitation with purified proteins and cell lysates, domain mapping, in vitro competition assay |
Biochimie |
Low |
26545799
|
| 2015 |
Sgt1 heterozygous knockout suppresses Hras-mediated transformation in vitro and tumor formation in p53-/- MEFs; Sgt1 depletion destabilizes the EWS-FLI1 and PAX3-FOXO1 oncogenic fusion proteins in Ewing sarcoma and rhabdomyosarcoma cells, respectively. |
Sgt1 heterozygous knockout mouse, in vitro transformation assay, siRNA knockdown, protein stability assay |
Oncogenesis |
Medium |
25985210
|