| 2008 |
KCTD5 interacts specifically with Cullin3 via its BTB domain plus additional N-terminal residues, binds ubiquitinated proteins, and forms oligomers through its BTB domain, establishing it as a putative substrate-specific adaptor for Cullin3-based E3 ligases. KCTD5 was found in the cytosol of cultured cell lines. |
Co-immunoprecipitation, binding assays, mutagenesis of BTB/N-terminal residues, subcellular fractionation |
The FEBS journal |
Medium |
18573101
|
| 2023 |
KCTD5 assembles as a pentamer and, in complex with Cullin3, ubiquitinates Gβγ subunits; cryo-EM structure shows five copies of Gβγ engaged symmetrically through KCTD5's C-terminal domain, enabling simultaneous ubiquitin transfer from the E2 enzyme to five Gβγ subunits. KCTD5-mediated Gβγ ubiquitination negatively regulates cAMP signaling downstream of GPCRs. |
Cryo-electron microscopy structure determination, ubiquitination assays, cAMP signaling assays |
Science advances |
High |
37450587
|
| 2024 |
Cryo-EM structure of the 5:5:5 KCTD5/CUL3NTD/Gβ1γ2 assembly reveals a highly dynamic complex with >60° rotational freedom between BTB and CTD moieties; CRL3KCTD5 engages the E3 ligase ARIH1 in an E3-E3 superassembly to ubiquitylate Gβγ, with conformational states positioning the ARIH1~ubiquitin thioester bond within ~10 Å of Lys-23 of Gβ as likely priming complexes. |
Cryo-EM structure determination, ubiquitylation assays, structural modeling of full-length CUL3/RBX1/ARIH1~ubiquitin conjugate |
Proceedings of the National Academy of Sciences of the United States of America |
High |
38625940
|
| 2015 |
KCTD5 interacts with MCM7, ZNF711, and FAM193B, forming trimeric complexes with Cullin3; however, KCTD5/Cullin3 did not induce polyubiquitylation or proteasome-dependent degradation of these partners. Instead, KCTD5 or Cullin3 overexpression increased ZNF711 protein stability, suggesting a role in protein stabilization rather than degradation for some substrates. |
Yeast two-hybrid, co-immunoprecipitation in mammalian cells, proteasome inhibitor assays, overexpression experiments |
Biochemical and biophysical research communications |
Medium |
26188516
|
| 2015 |
Molecular dynamics simulations of KCTD5 reveal that the pentameric CTD assembly is intrinsically stable, and that large interdomain twisting motions between the BTB and CTD domains are pivoted by a single hinge residue (Ser150), potentially positioning substrates for ubiquitination. |
Molecular dynamics simulations (120 ns) of full-length KCTD5 pentamer |
Journal of biomolecular structure & dynamics |
Low |
26336981
|
| 2018 |
KCTD5 physically interacts with ΔNp63α, and the Cullin3/KCTD5 complex induces monoubiquitination (not polyubiquitination) of ΔNp63α, reducing its DNA-binding affinity and impairing both its transactivation and transinhibitory activities, thereby attenuating ΔNp63α-driven cell proliferation. |
Co-immunoprecipitation, ubiquitination assays, DNA-binding assays, reporter/transactivation assays, cell proliferation assays |
FEBS letters |
Medium |
29782646
|
| 2020 |
KCTD5 binds RhoGDI1 and increases its interaction with CUL3; ectopic KCTD5 expression increases RhoGDI1 ubiquitination, whereas KCTD5 knockdown stabilizes RhoGDI1 and reduces its ubiquitination, establishing CUL3/KCTD5 as an E3 ligase complex that targets RhoGDI1 for degradation. |
Co-immunoprecipitation, ubiquitination assays, RNA interference knockdown, dominant-negative CUL3 expression, stability assays |
Journal of microbiology and biotechnology |
Medium |
32876072
|
| 2020 |
CRISPR/Cas9 and shRNA depletion of KCTD5 in B16-F10 cells increases cell migration, cell spreading, and focal adhesion disassembly rate. These effects are mediated through Rac1 GTPase activity (dominant-negative Rac1 rescues spreading) and Ca2+ signaling (KCTD5 loss decreases serum-induced Ca2+ response; ionomycin reversal restores focal adhesion size). |
CRISPR/Cas9 knockout, shRNA knockdown, live-cell imaging, dominant-negative Rac1 expression, Ca2+ imaging, focal adhesion dynamics assays |
Cells |
Medium |
33053687
|
| 2017 |
KCTD5 itself is ubiquitinated and degraded by the proteasome in AGS gastric epithelial cells; H. pylori infection impairs KCTD5 ubiquitination, reducing KCTD5 levels. Decreased KCTD5 (an adaptor of Cullin-3) increases H. pylori adherence, indicating KCTD5 proteasomal turnover is exploited by the pathogen to facilitate colonization. |
Ubiquitination assays, proteasome inhibitor experiments, H. pylori infection assays, RNA interference knockdown, adherence assays |
Frontiers in cellular and infection microbiology |
Medium |
29114497
|
| 2023 |
KCTD5 forms hetero-oligomeric complexes with numerous other KCTD family members (including KCTD2, KCTD17, and others); different regions of KCTD5 contribute distinctly to interactions with different KCTD partners. |
Co-immunoprecipitation, BRET (bioluminescence resonance energy transfer) in live cells, IP-luminescence domain-mapping assays |
International journal of molecular sciences |
Medium |
37762619
|
| 2024 |
KCTD5 is identified as a key stabilizing factor for Ikaros transcription factor; etoposide treatment decreases the KCTD5-Ikaros interaction, leading to accelerated Ikaros protein degradation (affecting IK1, IK2, IK4 isoforms but not IK6/IK7) in leukemic cells. |
Immunoprecipitation coupled with LC-MS/MS, co-immunoprecipitation, protein stability/degradation assays, etoposide treatment experiments |
Biological chemistry |
Medium |
38424700
|
| 2025 |
Conditional knockout of Kctd5 in striatal neurons in mice leads to dystonic phenotype, coordination deficits, and augmented electrically evoked cAMP responses to dopaminergic stimulation. Rescue by a Gβγ-scavenging nanobody confirms KCTD5 acts as a brake on Gβγ-mediated cAMP signaling in striatal circuits, and motor deficits are partially rescued by pharmacological antagonism of the indirect striatal cAMP pathway. |
Conditional knockout mouse (Cre-lox), 2-photon cAMP biosensor imaging, Gβγ-scavenging nanobody rescue, pharmacological rescue, behavioral assays |
PLoS biology |
High |
40233107
|
| 2025 |
Heterozygous Kctd5 knockout mice (Kctd5-/- embryos are lethal in early embryonic development) exhibit abnormal lipid metabolism including elevated cholesterol and triglycerides; genome-wide expression analysis suggests KCTD5 affects the PPAR signaling pathway and expression of Apolipoprotein family genes to regulate lipid metabolism. |
CRISPR/Cas9 heterozygous knockout mice, metabolic profiling, genome-wide gene expression analysis |
The international journal of biochemistry & cell biology |
Low |
40846050
|
| 2026 |
KCTD5 acts as a positive regulator of TRPM4 channel activity, increasing Ca2+ sensitivity; peptides designed to disrupt the TRPM4-KCTD5 protein-protein interface reduce TRPM4-dependent Na+ influx and currents and decrease cell invasion in MDA-MB-231 cells, confirming the functional importance of this interaction. |
BiFC (bimolecular fluorescent complementation), patch clamp electrophysiology, intracellular Na+ recordings, CRISPR KCTD5 knockout cells (HEK293KCTD5-/-), cell invasion assays |
Journal of chemical information and modeling |
Medium |
42214084
|