| 2009 |
SRBC/cavin-3 (CAVIN3) co-immunoprecipitates with caveolin-1, and a leucine zipper in SRBC is essential for both co-precipitation with caveolin-1 and localization to caveolae. SRBC binds PKCδ as a member of the STICK superfamily. SRBC remains associated with caveolin when caveolae bud to form vesicles (cavicles) that travel on microtubules, and in the absence of SRBC, intracellular cavicle traffic is markedly impaired. |
Co-immunoprecipitation, leucine zipper mutagenesis, live-cell imaging of cavicle trafficking |
The EMBO journal |
High |
19262564
|
| 2013 |
Cavin-3 dictates the balance between ERK and Akt signaling: loss of cavin-3 increases Akt signaling at the expense of ERK, while gain of cavin-3 increases ERK signaling at the expense of Akt. Cavin-3 facilitates ERK signaling by anchoring caveolae to the membrane skeleton via myosin-1c; loss of this linkage reduces caveolae abundance and separates the ERK activation module from signaling receptors. Loss of cavin-3 also promotes Akt signaling through suppression of EGR1 and PTEN. In vivo consequences of cavin-3 knockout include increased lactate production and cachexia. |
Cavin-3 knockout mice, in vitro gain/loss-of-function, co-immunoprecipitation with myosin-1c, signaling pathway analysis (ERK/Akt phosphorylation), metabolic assays |
eLife |
High |
24069528
|
| 2012 |
CAVIN-3 is a cytoplasmic PER2-interacting protein that influences circadian clock properties. Loss- and gain-of-function of CAVIN-3 shortened and lengthened, respectively, the circadian period in fibroblasts, and affected PER:CRY protein abundance and interaction. CAVIN-3 required its PKCδ-binding site to exert its effect on period length. Depletion of PKCδ alone had little effect, suggesting involvement of yet-uncharacterized kinases. CAVIN-3 activity in circadian gene expression was independent of caveolae. |
Co-immunoprecipitation (PER2 interaction), RNAi knockdown, overexpression, circadian period assays in fibroblasts, PKCδ-binding site mutagenesis |
EMBO reports |
Medium |
23079727
|
| 2015 |
Cavin3 is targeted to caveolae by cavin1, where it interacts with the scaffolding domain of caveolin1 and promotes caveolae dynamics. The N-terminal region of cavin3 binds a trimer of the cavin1 N-terminus in competition with a homologous cavin2 region, indicating that cavins form distinct subcomplexes through their N-terminal regions. Cavin3 is enriched at deeply invaginated caveolae, and loss of cavin3 increases the proportion of stable caveolae and decreases short-lived caveolae at the membrane. |
Co-immunoprecipitation, truncation/domain mapping, live-cell TIRF imaging of caveolae dynamics, siRNA knockdown |
Journal of cell science |
High |
25588833
|
| 2008 |
hSRBC (CAVIN3) increases p53 protein stability and expression of p53 target genes (p21Waf1, PUMA, NOXA). hSRBC-mediated cell cycle arrest and apoptosis were abolished by blockade of p53 function. Stable expression of hSRBC led to G1 cell cycle arrest, apoptosis, suppressed colony forming ability and xenograft tumor growth, and elevated sensitivity to genotoxic agents. |
Stable and transient overexpression, p53 functional blockade, xenograft tumor assay, western blot for p53 target genes |
International journal of cancer |
Medium |
18059034
|
| 2011 |
PRKCDBP (CAVIN3) gene transcription is directly activated by NF-κB in response to TNFα: luciferase reporter and ChIP assays demonstrate that TNFα-induced PRKCDBP promoter activity requires an intact κB site, and RelA transfection enhances PRKCDBP expression. PRKCDBP induction correlates with tumor cell sensitivity to TNFα-induced apoptosis. |
Luciferase reporter assay, chromatin immunoprecipitation (ChIP), RelA transfection, siRNA knockdown, xenograft assay |
Clinical cancer research |
High |
21980136
|
| 2019 |
ROR1 binds CAVIN3 at a site distinct from those for CAV1 and CAVIN1; this interaction is required for proper CAVIN3 subcellular localization and caveolae-dependent endocytosis but not caveolae formation itself. The ROR1-CAVIN3 interaction facilitates caveolae trafficking linked to pro-survival AKT signaling from early endosomes in lung adenocarcinoma cells. |
Co-immunoprecipitation, domain mapping, siRNA knockdown, endocytosis assays, subcellular fractionation/localization, AKT signaling readouts |
Oncogene |
Medium |
30894682
|
| 2021 |
Cavin3 is released from caveolae upon UV and mechanical stress-induced caveolae disassembly and directly interacts with BRCA1. Cavin3 deletion downregulates BRCA1 and BRCA1 A-complex components. Cavin3 sensitizes cancer cells to UV-induced apoptosis, and cavin3-deficient cells are sensitive to PARP inhibition; concomitant depletion of 53BP1 restored BRCA1-dependent sensitivity to PARP inhibition, placing cavin3 in the BRCA1 DNA repair pathway. |
Genome editing (CRISPR KO), label-free quantitative proteomics, cell-free expression interaction assays, RNAi depletion, UV-apoptosis assays, PARP inhibitor sensitivity, genetic epistasis (53BP1/BRCA1 double depletion) |
eLife |
High |
34142659
|
| 2014 |
In cavin-3 knockout mice, loss of cavin-3 does not significantly affect caveolae abundance in adipose tissue or other widely studied tissues, and has no effect on body composition or glucose tolerance, indicating cavin-3 is not absolutely required for caveolae formation in these contexts. |
Cavin-3 knockout mouse generation, electron microscopy for caveolae counting, metabolic phenotyping (body weight, fat mass, glucose tolerance tests), microarray |
PloS one |
Medium |
25036884
|
| 2017 |
Loss of cavin-3 in smooth muscle reduces cavin-1 protein levels by ~40% and reduces caveolae density by 40–45% in vascular and urinary bladder smooth muscle (but not in endothelial cells), demonstrating a tissue-specific role for cavin-3 in caveolae maintenance in smooth muscle. Enhanced nitric-oxide-dependent vascular relaxation was observed alongside elevated soluble guanylyl cyclase expression in KO mice. |
Cavin-3 knockout mice, electron microscopy (caveolae quantification), vascular contraction/relaxation assays, western blot for cavin-1/sGC protein levels |
Cell and tissue research |
Medium |
28285351
|
| 2014 |
Cavin-3 overexpression in HT1080 fibrosarcoma cells reduces cell migration and inhibits PMA-induced MMP-9 secretion and gene expression, in part through prevention of AKT dephosphorylation. Cavin-3 gene silencing increases MMP-9 expression and secretion, establishing a cavin-3/AKT/MMP-9 signaling axis. |
Cavin-3 overexpression and siRNA knockdown, MMP-9 zymography/ELISA, cell migration assay, AKT phosphorylation western blot, PMA stimulation |
Cancer growth and metastasis |
Medium |
25520561
|
| 2020 |
Cavin-3 knockdown impairs adipocyte differentiation; its overexpression accelerates adipogenesis. Mechanistically, Cavin-3 modulates TACE (ADAM17)-mediated shedding of Pref-1 (preadipocyte factor-1), a known inhibitor of adipogenesis. Cavin-3 silencing markedly increases Pref-1 during adipocyte maturation while decreasing expression of adipogenesis genes (PPARγ, FAS, aP2, Adipoq). |
Stable knockdown/overexpression cell lines, qRT-PCR, western blot, confocal immunofluorescence, TACE activity assay, adipogenesis assays |
International journal of molecular sciences |
Medium |
32679831
|
| 2020 |
Human parainfluenza virus type 2 (hPIV-2) V protein binds directly to Cavin3 (N-terminal region of Cavin3 and Trp residues in C-terminal region of V protein are required), inhibits Cavin3 proteasomal degradation, increases Cavin3 abundance in lipid raft microdomains, and thereby facilitates viral assembly and budding. Cavin3 knockdown suppresses hPIV-2 growth without affecting viral entry, replication, transcription, or translation. |
Co-immunoprecipitation, pulse-chase proteasomal degradation assay, V protein overexpression, siRNA knockdown, viral growth assays, lipid raft fractionation |
Frontiers in microbiology |
Medium |
32425917
|
| 2025 |
CAVIN3 deficiency in endothelial cells inhibits ERK phosphorylation, which downregulates Jagged 1 (JAG1) expression, thereby promoting vascular normalization in pathological neovascularization. Transcription factor ZEB1 regulates CAVIN3 transcription in endothelial cells under hypoxic conditions. CAVIN3 knockdown disrupts EC proliferation and vascular sprouting, restores pericyte-EC interactions. |
siRNA knockdown in endothelial cells, in vivo CNV and OIR mouse models, ERK phosphorylation western blot, JAG1 expression assays, ZEB1 ChIP/reporter assays, pericyte-EC co-culture |
JCI insight |
Medium |
40337864
|
| 2024 |
A phosphomimic mutation in a Thr-Ser pair proximal to the disordered C-terminal half of the Cavin1 HR1 coiled-coil domain selectively abolishes Cavin2 and Cavin3 association with Cavin1, revealing that phosphorylation near this region regulates the formation of Cavin1-Cavin2 and Cavin1-Cavin3 subcomplexes. |
Nanobody development, X-ray crystal structure of nanobody-HR1 complex, phosphomimic mutagenesis, co-immunoprecipitation |
bioRxivpreprint |
Medium |
bio_10.1101_2024.11.26.625551
|
| 2023 |
PRKCDBP promotes pyroptosis by activating the NLRP3 inflammasome, resulting in cleavage of CASP1, IL-1β, and GSDMD in NSCLC cells. PRKCDBP is upregulated through a ceRNA mechanism in which lncRNA TCONS-14036 sequesters miR-1228-5p, relieving miR-1228-5p-mediated suppression of PRKCDBP. |
Flow cytometry, TUNEL assay, ASC speck formation, ELISA, dual-luciferase reporter assay, RNA immunoprecipitation, western blot, siRNA/overexpression |
Cell proliferation |
Medium |
36696967
|