| 2004 |
Rpn7 (PSMD6 ortholog in yeast) is required for the structural integrity of the 26S proteasome; temperature-sensitive rpn7-3 mutant cells accumulate poly-ubiquitinated proteins and stabilize ubiquitin-proteasome substrates (N-end rule, UFD pathway substrates, cell cycle regulators Pds1 and Clb2). Analysis showed the lid subcomplex in rpn7-3 cells contained only 5 of 8 lid components, indicating Rpn7 is required for correct lid structure and 26S holoenzyme assembly. |
Temperature-sensitive yeast mutant analysis, affinity purification of 26S proteasome, substrate stabilization assays (beta-galactosidase reporters), immunoblotting |
The Journal of biological chemistry |
High |
15102831
|
| 2006 |
The 26S proteasome modules (core particle, base, and lid) can be formed and imported into the yeast nucleus independently of each other. In rpn7-3 mutant cells at restrictive temperature, lid formation was specifically disrupted while an intact base was produced and localized to the nucleus, establishing that Rpn7 is specifically required for lid assembly and not for base or core particle formation. |
Biochemical characterization and microscopic localization of proteasome in yeast lid mutants (rpn5-1, rpn7-3) and base mutant (ΔN rpn2); subcellular fractionation and fluorescence microscopy |
Molecular biology of the cell |
High |
17135287
|
| 2007 |
Human DSS1 (Sem1) interacts with the proteasome subunits RPN3 and RPN7 (PSMD6) in human tumor cells; BRCA2 also interacts with RPN3 and RPN7; the BRCA2/RPN7 interaction is independent of DSS1. Defined regions of DSS1 are important for interactions with RPN3, RPN7, and BRCA2. |
Co-immunoprecipitation, domain mapping/deletion analysis in human tumor cell lines |
Oncogene |
Medium |
17563742
|
| 2007 |
A conserved leucine residue in the PCI domain of Rpn7 (PSMD6 ortholog in fission yeast) is critical for protein function; replacing it with aspartate inactivated Rpn7 and abolished high-affinity binding to Rpn9. Rpn7 and Rpn5 bind Rpn9 with high affinity via their PCI domains, and this interaction is disrupted by the leucine-to-aspartate mutation. |
High-copy suppressor screen, site-directed mutagenesis of PCI domain leucine residue, protein-binding assays in S. pombe |
The Journal of biological chemistry |
Medium |
17761670
|
| 2010 |
Dissection of lid assembly using yeast rpn7-3, Δrpn9, and rpn12-1 mutants identified lid subassemblies including an Rpn3-Rpn7 pair and a lid-like complex lacking Rpn12 by mass spectrometry, demonstrating that the lid assembles in an ordered, multi-step process: first a core module (Rpn5, 6, 8, 9, 11) forms, then a second module consisting of Rpn3, Rpn7 (PSMD6 ortholog), and Sem1 is attached, followed by Rpn12 incorporation. |
Yeast lid mutant analysis, affinity purification, mass spectrometry identification of subassemblies |
Biochemical and biophysical research communications |
High |
20471955
|
| 2010 |
Psmd6 (zebrafish ortholog) is required for cell proliferation of lens epithelium and for proper elongation and differentiation of lens fiber cells. Loss of psmd6 in the volvox mutant causes accumulation of polyubiquitylated proteins, and the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase is involved in the lens defects, placing Psmd6 in the ubiquitin-proteasome pathway upstream of APC/C substrate degradation during lens development. |
Zebrafish volvox mutant characterization, genetic mapping to psmd6, polyubiquitylation assays, epistasis with APC/C |
Development (Cambridge, England) |
High |
20724448
|
| 2012 |
The 19S subunit Rpn7 (PSMD6) undergoes increased protein levels and nuclear translocation in response to DNA damage. Rpn7 colocalizes with DNA damage foci throughout their lifespan. Silencing of Rpn7 promotes faster resolution of DNA damage foci and specifically decreases long-lived foci frequencies without affecting repair of short-lived foci, indicating Rpn7 stabilizes DNA damage foci and enables senescence following genotoxic insult. |
siRNA knockdown, immunofluorescence colocalization with DNA damage foci markers, foci lifespan analysis, subcellular fractionation (nuclear translocation) |
IUBMB life |
Medium |
22473755
|
| 2013 |
The C-terminal helix of Sem1 (DSS1, the mammalian ortholog partner) binds to the PCI domain of Rpn7 (PSMD6 ortholog) within the 26S proteasome. Cryo-EM single-particle reconstruction of proteasomes from sem1-deletion yeast localized this interaction, and site-specific cross-linking data indicated the N-terminal region of Sem1 bridges the cleft between Rpn7 and Rpn3, with Sem1 acting as molecular glue stabilizing the Rpn3/Rpn7 heterodimer. |
Cryo-EM single particle reconstruction, sem1 deletion yeast strains, site-specific cross-linking |
Biochemical and biophysical research communications |
High |
23643786
|
| 2014 |
Sem1 (DSS1 in mammals) enforces ordered incorporation of subunits Rpn3 and Rpn7 (PSMD6 ortholog) into the assembling proteasome lid by grasping both using conserved acidic segments separated by a flexible linker. TEV protease cleavage of Sem1 showed that its tethering function is important for biogenesis and integrity of the Rpn3-Sem1-Rpn7 ternary complex but becomes dispensable once the ternary complex is incorporated into larger lid precursors. |
In vitro reconstitution, TEV protease-cleavage site engineering into Sem1, biochemical assembly assays, domain mutagenesis |
Molecular cell |
High |
24412063
|
| 2014 |
PSMD6 undergoes DNA damage-induced phosphorylation, nuclear import, and recruitment to proteasome at DNA damage sites; these events are mediated by urokinase-type plasminogen activator receptor (uPAR) signaling in vascular smooth muscle cells. uPAR is essential for functional assembly of the 26S proteasome, and deficiency of uPAR or PSMD6 delays DNA repair and reduces cell survival. |
uPAR knockdown, phosphorylation assays, subcellular fractionation (nuclear import), colocalization/immunofluorescence, cell survival assays in vascular smooth muscle cells |
PloS one |
Medium |
24987841
|
| 2015 |
Rpn11 plays a key role in bridging lid module 1 and module 2 subunits; module 2 includes Rpn3, Rpn7 (PSMD6 ortholog), Rpn12, and Rpn15. Suppression of RPN11 halted lid assembly but allowed base and 20S CP to pre-assemble. Re-introducing the C-terminal portion of Rpn11 enabled recruitment of missing module 2 subunits including Rpn7, and module 1 was reconstituted in vitro stepwise. |
RPN11 expression suppression, mutant proteasome isolation, in vitro module reconstitution, protein interaction assays |
Bioscience reports |
Medium |
26182356
|
| 2021 |
AT1R colocalizes with PSMD6 (used as a proteasomal marker) in aortic cells, and this colocalization is reduced after SNX1 knockdown. Proteasomal inhibition (not lysosomal) increases AT1R protein content and this is accompanied by decreased ubiquitin/AT1R binding after SNX1 knockdown, suggesting PSMD6-containing 26S proteasome mediates SNX1-directed degradation of AT1R. |
Confocal colocalization microscopy (PSMD6 and AT1R), proteasomal vs. lysosomal inhibitor treatment, cycloheximide chase assay, SNX1 siRNA knockdown in A10 cells |
Hypertension research |
Low |
33972750
|
| 2023 |
PSMD6 (Rpn7) tagged with mScarlet at the endogenous locus colocalizes with YFP-tagged PSMB6 (20S CP subunit) in cells, predominantly with nuclear accumulation. Under osmotic stress, nuclear proteasomal granules are positive for both tags. Upon PSMD1 knockdown (which increases free 20S CPs), 20S-YFP remained nuclear while PSMD6-mScarlet redistributed to cytoplasm, demonstrating distinct subcellular distribution of 19S RP (containing PSMD6) versus uncapped 20S CPs. |
CRISPR endogenous YFP/mScarlet tagging of PSMB6 and PSMD6, live-cell fluorescence colocalization microscopy, osmotic stress treatment, PSMD1 siRNA knockdown |
Biomolecules |
Medium |
37371572
|
| 2025 |
CRISPR-based loss of psmd6 in zebrafish leads to defects in heart development including dysmorphic hearts, myocardial cell blebbing, and reduced outflow tracts, as well as deficits in cardiac function. PPI network analysis placed PSMD6 in a subnetwork with known CHD genes and other proteasome factors (POMP, PSMA6, PSMA7, PSMD3), indicating a role for proteasome function in cardiac morphogenesis. |
CRISPR targeting and mutant zebrafish strain generation for psmd6, cardiac morphology and function assessment, PPI network analysis |
PLoS genetics |
Medium |
40857331
|