| 1999 |
DDA3 (PSRC1) was identified as a p53-regulated gene: DDA3 mRNA is transcriptionally induced by p53 in a cycloheximide-insensitive, actinomycin D-sensitive manner, indicating direct transcriptional activation without requiring de novo protein synthesis. Overexpression of DDA3 suppressed colony formation in H1299 lung carcinoma cells. |
Differential mRNA display, actinomycin D/cycloheximide treatment, colony formation assay |
Oncogene |
Medium |
10618717
|
| 2002 |
Mouse DDA3 is a direct transcriptional target of both p53 and p73: a p53 response element (RE2) in the DDA3 gene was shown by luciferase reporter assay and gel mobility shift analysis to bind wild-type p53 and confer transactivation. DDA3 induction by DNA damage was absent in p53-knockout MEFs. p73 family members also transactivated DDA3 via RE2. |
Luciferase reporter assay, gel mobility shift assay, p53-knockout MEFs, overexpression |
Oncogene |
High |
12082536
|
| 2007 |
DDA3 is a microtubule-associated protein that interacts with plus-end binding protein EB3. Interaction was confirmed by GST pull-down and co-immunoprecipitation (requiring intact microtubules). Interaction domains were mapped to DDA3 aa 118–241 and 242–329 (EB3 binding and MT-bundling) and EB3 N- and C-termini. DDA3 directly binds microtubules in vitro and cooperates with EB3 for MT binding. DDA3 also interacts with APC2. Ectopic expression of DDA3 and EB3 enhanced beta-catenin-dependent transactivation and cyclin D1; knockdown inhibited beta-catenin signaling and colony formation. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, in vitro microtubule-binding assay, immunofluorescence, reporter assay, siRNA knockdown |
Oncogene |
High |
17310996
|
| 2008 |
Human DDA3 is transcriptionally repressed by p53 (opposite to mouse DDA3): p53 binds three consensus El-Deiry decamers at −1478/−1403 of the hDDA3 promoter as shown by chromatin immunoprecipitation, and luciferase analysis showed this region mediates p53-dependent repression. hDDA3 mRNA and protein are suppressed in DNA-damaged cells in a wild-type p53-dependent manner. |
Chromatin immunoprecipitation (ChIP), luciferase reporter assay, Western blot, real-time PCR |
Biochemical and biophysical research communications |
High |
18291097
|
| 2008 |
DDA3 recruits microtubule depolymerase Kif2a to the mitotic spindle and spindle poles in a microtubule-dependent manner. DDA3 depletion causes unaligned chromosomes, reduced inter-kinetochore tension, decreased anaphase chromosome velocity, increased spindle MT steady-state levels, reduced MT turnover, and increased MT polymerization rate — phenocopying partial Kif2a knockdown. |
siRNA depletion, mass spectrometry (co-purification), immunofluorescence, live imaging, fluorescence recovery after photobleaching (FRAP) |
The Journal of cell biology |
High |
18411309
|
| 2008 |
DDA3 interacts with ASPP2 (a p53-binding protein). The interaction domain on DDA3 maps to aa 118–241; both N- and C-terminal regions of ASPP2 bind DDA3. DDA3 dose-dependently inhibits ASPP2-stimulated p53-mediated BAX promoter activation without interfering with ASPP2–p53 binding. |
Yeast two-hybrid screening, GST pull-down, immunofluorescence colocalization, luciferase reporter assay |
Biochemical and biophysical research communications |
Medium |
18793611
|
| 2009 |
Domain analysis of DDA3: the C-terminal domain directly binds microtubules in vitro and associates with the mitotic spindle in vivo; the N-terminal domain does not bind MTs but acts dominant-negatively, preventing endogenous DDA3 spindle association and reducing spindle-associated Kif2a while increasing spindle MT density. |
In vitro microtubule-binding assay, dominant-negative overexpression, immunofluorescence, live imaging |
Cell cycle |
Medium |
19738423
|
| 2010 |
DDA3 is phosphorylated on Ser225 during mitosis. The phospho-mimicking S225D variant rescues DDA3-knockdown mitotic defects (unaligned chromosomes), whereas the non-phosphorylatable S225A mutant does not, demonstrating that Ser225 phosphorylation is required for DDA3's mitotic function. |
Mass spectrometry (phosphosite identification), phospho-mimicking and non-phosphorylatable mutants, siRNA rescue assay, immunofluorescence |
Biochemical and biophysical research communications |
Medium |
20117088
|
| 2011 |
DDA3 interacts with MCAK (a plus-end MT depolymerase) and localizes to kinetochores. DDA3 depletion causes CENP-E accumulation at kinetochores of unaligned chromosomes; Aurora B kinase activity and chromosomal passenger complex localization are unaffected by DDA3 depletion. |
Co-immunoprecipitation, immunofluorescence, siRNA depletion |
Biochemical and biophysical research communications |
Medium |
21426902
|
| 2011 |
Mitotic kinases phosphorylate DDA3 at Ser22, Ser65, Ser70, and Ser223 (identified by mass spectrometry). Unphosphorylated DDA3 has both MT-polymerizing and MT-bundling activities; phospho-mimetic mutants at these sites lose both activities while retaining MT-binding. Cdk1 and Aurora A phosphorylation negatively regulate MT-polymerizing/bundling activities in vitro; Plk1 does not. Sequential phosphorylation by Aurora A and Plk1 inhibits phosphorylation by other kinases. |
Mass spectrometry (phosphosite identification), in vitro kinase assay, phospho-mimicking mutants, in vitro MT polymerization and bundling assays |
Biochemical and biophysical research communications |
High |
21473853
|
| 2012 |
DDA3 bundles and stabilizes microtubules in vivo and in vitro; overexpression increases acetylated and tyrosinated microtubule abundance. DDA3 overexpression suppresses neurite/axon outgrowth in PC12, N2a, and hippocampal neurons, while its depletion accelerates neurite/axon formation. DDA3 knockdown reduces β3-tubulin levels contributing to spontaneous neuritogenesis. DDA3 is downregulated during neuronal differentiation. |
Overexpression, siRNA knockdown, in vitro MT bundling/stabilization assays, immunofluorescence, PC12/N2a/hippocampal neuron cell culture, Western blot |
Journal of cell science |
High |
22467851
|
| 2013 |
DDA3 interacts with EB1 via an SxIP motif in its C-terminal Pro/Ser-rich region, enabling MT plus-end loading and tracking in an EB1-dependent manner (shown by TIRF microscopy and time-lapse imaging). EB1-dependent loading of DDA3 stabilizes MT plus-ends at the cell cortex and facilitates directional cell migration. EB1 acetylation potentially regulates the DDA3–EB1 interaction and EGF-elicited cell migration. |
Biochemical interaction mapping, TIRF microscopy, time-lapse imaging, siRNA knockdown, EGF stimulation |
Scientific reports |
High |
23652583
|
| 2016 |
ASB7 (a Cullin 5–SOCS box E3 ligase) ubiquitinates DDA3 and targets it for proteasomal degradation. Microtubule presence prevents the ASB7–DDA3 interaction, stabilizing DDA3. ASB7 knockdown increases DDA3 levels, increases Kif2a recruitment to the spindle, reduces MT polymerization, and causes unaligned chromosomes — a phenotype rescued by DDA3 deletion. |
Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, genetic epistasis (double knockdown rescue), immunofluorescence |
The Journal of cell biology |
High |
27697924
|
| 2016 |
Mdp3 (MAP7D3) forms a complex with DDA3 and inhibits DDA3-mediated Kif2a recruitment to the mitotic spindle. Mdp3 depletion leads to aberrant Kif2a activity at the MT minus end, decreased spindle stability, unaligned chromosomes, lagging chromosomes, and chromosome bridges. DDA3 and Mdp3 act oppositely on minus-end MT dynamics but do not affect each other's localization. |
Co-immunoprecipitation, siRNA knockdown, immunofluorescence, live imaging |
Journal of cell science |
High |
27284004
|
| 2016 |
ANKRD53 interacts with DDA3 (identified by proteomic analysis) and is recruited to the mitotic spindle by DDA3. ANKRD53 counteracts DDA3 activity for spindle MT polymerization. ANKRD53 depletion delays mitosis, increases unaligned chromosomes, decreases spindle MT polymerization, activates the spindle assembly checkpoint, and causes bi-nuclei and polylobed nuclei. |
Proteomic/MS analysis, co-immunoprecipitation, siRNA knockdown, immunofluorescence |
Biochemical and biophysical research communications |
Medium |
26820536
|
| 2016 |
Ska1 is recruited to kinetochores by DDA3 to stabilize end-on kinetochore–MT attachment. After Kif2a is recruited to the spindle by DDA3, Ska1 targets Kif2a to the minus-end of spindle MTs to facilitate spindle dynamics. These interactions provide a molecular link between spindle dynamics and kinetochore composition. |
Co-immunoprecipitation, siRNA knockdown, immunofluorescence, rescue experiments |
Biochemical and biophysical research communications |
Medium |
26797278
|
| 2018 |
PSRC1 overexpression in macrophages reduces cellular cholesterol content, increases cholesterol efflux, and inhibits foam cell formation by upregulating PPARγ and LXRα expression. In apoE−/− mice, adenoviral PSRC1 overexpression inhibits atherosclerotic lesion development, decreases plasma TC/TG/LDL-C/inflammatory cytokines, and increases HDL-C. The β-catenin pathway (upstream of PPARγ and LXRα) is elevated in PSRC1-overexpressing liver and macrophages; NF-κB activity is decreased. |
Adenoviral overexpression in RAW264.7 cells and apoE−/− mice, cholesterol efflux assay, Western blot, ELISA, histology |
Journal of molecular and cellular cardiology |
Medium |
29378206
|
| 2019 |
c-Cbl acts as an E3 ubiquitin ligase that degrades DDA3. c-Cbl depletion increases DDA3 protein levels, leading to increased Kif2a recruitment to the spindle, reduced spindle formation, chromosome alignment defects, centrosome over-duplication, and centriole amplification. |
siRNA knockdown, Western blot, immunofluorescence, co-immunoprecipitation (implied by E3 ligase assay) |
Molecules and cells |
Medium |
31722512
|
| 2022 |
PSRC1 deletion in macrophages impairs reverse cholesterol transport and enhances cholesterol uptake and inflammation. PSRC1 overexpression in macrophages overexpressing PSRC1 rescues proatherogenic phenotype in TMAO-stimulated cells, partly attributed to sulfotransferase 2B1b (SULT2B1b) inhibition. PSRC1 overexpression in vitro inhibited FMO3 expression, and this effect was rescued by an ERα inhibitor, indicating ERα-mediated regulation. |
PSRC1 knockout/overexpression in macrophages, reverse cholesterol transport assay, hepatic RNA-seq, ERα inhibitor rescue, in vitro overexpression |
Journal of molecular and cellular cardiology |
Medium |
35690006
|
| 2022 |
PSRC1 deletion enriches TMA-producing gut bacteria, enhances plasma TMAO and betaine production, upregulates hepatic FMO3 expression, and promotes a proinflammatory colonic phenotype. Fecal microbiota transplant from PSRC1-KO mice to apoE−/− recipients elevated TMAO, plaque lipid deposition, and macrophage accumulation. PSRC1 overexpression in vitro inhibits FMO3 via an ERα-dependent mechanism. |
PSRC1-KO mice, metagenomics, untargeted metabolomics, hepatic RNA-seq, fecal microbiota transplant, antibiotic treatment, in vitro overexpression with ERα inhibitor |
Gut microbes |
Medium |
35613310
|
| 2025 |
PSRC1 is localized to spindle poles throughout all stages of mouse oocyte meiosis, co-localizing with spindle microtubules (confirmed by Taxol/nocodazole treatment). Psrc1 knockdown causes abnormal spindle morphology, sustained spindle assembly checkpoint activation, abnormal kinetochore–microtubule attachments, and increased aneuploidy. Both knockdown and overexpression of Psrc1 cause abnormal spindle assembly and increased large polar body rates. |
siRNA knockdown, mRNA overexpression, immunofluorescence, Taxol/nocodazole treatment, Western blot |
FASEB journal |
Medium |
40810374
|