| 1994 |
PSMC4 (TBP7) was identified as subunit 6 (S6) of the 26S protease from human erythrocytes, establishing it as an integral ATPase component of the 26S proteasome regulatory complex. |
SDS-PAGE, CNBr peptide mapping, internal peptide sequencing, and sequence comparison with known proteins |
Biological chemistry Hoppe-Seyler |
High |
8060531
|
| 1996 |
PSMC4 (MIP224/TBP7) interacts specifically with MB67, an orphan nuclear hormone receptor, and coexpression of MIP224 inhibits transactivation by MB67 in mammalian cells. This interaction was also detected with other CAD-containing proteins (MSS1, TRIP1) in yeast. |
Yeast two-hybrid screen, coexpression transactivation assay in mammalian cells |
The Journal of steroid biochemistry and molecular biology |
Medium |
8603043
|
| 1996 |
The N-terminal region of PSMC4 (TBP7) contains a leucine zipper domain, and its central region contains four conserved ATPase motifs (Gx4GKT, DEID, SAT, H/QRxGRx2R) characteristic of ATP-dependent RNA/DNA helicases, with strictly conserved spacing between motifs across proteasomal ATPases. |
cDNA cloning and protein sequence analysis of rat TBP7 orthologue |
Biochemical and biophysical research communications |
Medium |
8607789
|
| 1998 |
PSMC4 (TBP7) gene was mapped to human chromosome 19q13.11-q13.13 by fluorescence in situ hybridization, and immunoblot analysis confirmed its association with the purified 26S proteasome. TBP7 showed heterogeneity in electrical charge. |
Fluorescence in situ hybridization (FISH), immunoblot analysis of purified 26S proteasome |
Biochemical and biophysical research communications |
Medium |
9473509
|
| 1999 |
PSMC4 (TBP7) and other proteasomal ATPases (MSS1, TBP1, SUG1, S4) form a complex with TATA-binding protein (TBP) and a novel transcriptional activator TIP120 (~800 kDa complex), but this TBP-ATPase complex is distinct from the 26S proteasome or its 19S regulatory unit. Direct TBP binding was demonstrated for SUG1 and S4 by far-Western; the remaining ATPases including TBP7 were found in the TIP preparations by 2-D electrophoresis and microsequencing. |
TBP pull-down, 2-D electrophoresis, far-Western analysis, protein microsequencing, Western blotting |
Genes to cells : devoted to molecular & cellular mechanisms |
Medium |
10526239
|
| 2000 |
Psmc4-deficient mice die before implantation with defective blastocyst development, demonstrating that PSMC4 is essential for early embryogenesis and has non-compensatory functions in vivo (not rescued by Psmc3). |
Gene targeting (knockout mice), embryonic lethality analysis |
Genomics |
High |
10945464
|
| 2000 |
PSMC4 (S6/TBP7) subunit of the 26S proteasome localizes to the heterochromatic region of nuclei in insect muscle fibres undergoing programmed cell death, as determined by immunogold electron microscopy, suggesting a nuclear role for this ATPase subunit during PCD. |
Immunogold electron microscopy on Manduca sexta intersegmental muscles |
Cell death and differentiation |
Medium |
11175258
|
| 2002 |
Gankyrin (a liver oncoprotein) interacts with the C-terminal 78 amino acids of PSMC4 (S6/TBP7) ATPase, both in its free form and when associated with the 19S regulatory complex. Overexpression of tagged gankyrin in cultured cells co-precipitates PSMC4 and endogenous CDK4, suggesting a trimeric complex. |
Yeast two-hybrid screen, deletional mutagenesis, co-immunoprecipitation from cultured cells, precipitation of tagged proteins |
The Journal of biological chemistry |
High |
11779854
|
| 2002 |
PSMC4 (Tbp7), an ATPase subunit of the 26S proteasome, co-immunoprecipitates with cytokeratin-8 (CK-8), ubiquitin, UBB+1, and proteasomal subunit beta5 in a high-molecular-weight complex associated with Mallory body formation. This complex increases upon incubation with ATP, suggesting active proteasomal engagement with cytokeratin aggregates. |
Cytokeratin-8 immunoprecipitation, Western blot, in vitro incubation with proteasomal fractions and ATP |
Experimental and molecular pathology |
Medium |
11784119 12231209
|
| 2007 |
PSMC4 (S6 ATPase/tbp7) directly interacts with synphilin-1 (an alpha-synuclein-interacting protein implicated in Parkinson's disease). Co-overexpression of PSMC4 and synphilin-1 leads to colocalization in aggresome-like inclusions, reduced proteasomal activity, and increased inclusion formation compared to synphilin-1 alone. PSMC4 was also identified as a component of Lewy bodies in PD patient brains. |
Yeast two-hybrid, co-immunoprecipitation, immunofluorescence colocalization, proteasome activity assay, immunohistochemistry in PD brain |
FASEB journal |
High |
17327361
|
| 2011 |
PSMC4 (TBP7), an AAA-ATPase 19S proteasomal subunit, directly interacts with TRAP1 (mitochondrial HSP90) in the endoplasmic reticulum (ER), not in mitochondria. TRAP1 and TBP7 colocalize in the ER as demonstrated by biochemical fractionation, confocal microscopy, and FRET analysis. TBP7 and/or TRAP1 silencing enhances protein ubiquitination and stress-induced cell death, and TRAP1 controls ubiquitination/degradation of specific nuclear-encoded mitochondrial proteins through this ER-localized interaction. |
Mass spectrometry interactome, co-immunoprecipitation, confocal microscopy, FRET, subcellular fractionation, shRNA silencing, ubiquitination assays |
Cell death and differentiation |
High |
21979464
|
| 2011 |
Nrf1 transcription factor drives expression of PSMC4 as a target gene. siRNA-mediated silencing of β-TrCP (which degrades Nrf1 in the nucleus) markedly augments PSMC4 expression, establishing PSMC4 as a downstream target of the Nrf1/β-TrCP regulatory axis. |
siRNA knockdown, gene expression analysis |
Molecular and cellular biology |
Medium |
21911472
|
| 2014 |
Muscle-specific deletion of Rpt3 (Psmc4) in mice causes profound muscle growth defects, decreased force production, dysregulated proteasomal activity, impaired autophagosome formation despite upregulated autophagy pathway, accumulation of basophilic inclusions, and sarcomere disorganization. This establishes PSMC4 as essential for maintaining myofiber integrity and muscle growth in vivo. |
Conditional knockout mice (muscle-specific Cre), histology, electron microscopy, proteasome activity assays, autophagy pathway analysis |
Journal of cell science |
High |
25380823
|
| 2013 |
The ER-localized TRAP1/TBP7 (PSMC4) complex controls ubiquitination and degradation of CDK1 (and MAD2). TRAP1 interacts with CDK1 and prevents its ubiquitination in cooperation with TBP7; this is the limiting step in TRAP1 regulation of G2-M cell cycle transition. |
Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, gene expression profiling, immunofluorescence |
Cell death & disease |
Medium |
24113185
|
| 2017 |
TRAP1 prevents CDK1 ubiquitination through cooperation with the proteasome regulatory particle TBP7 (PSMC4), establishing TBP7 as a co-factor in TRAP1-dependent quality control of CDK1 during G2-M transition. TRAP1 silencing causes enhanced CDK1 ubiquitination, failure of nuclear CDK1/cyclin B1 translocation, and MAD2 degradation. |
Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, CDK1 inhibitor rescue experiments, gene expression profiling in breast/colorectal/lung carcinoma cells and tumor specimens |
The Journal of pathology |
High |
28678347
|
| 2014 |
PSMC4 (26S proteasome regulatory subunit 6B) was identified by affinity pull-down and LC-MS/MS as a direct binding target of neuroprotective pyrazolone small molecules. Binding of these molecules to PSMC4 (and PSMC1) was associated with proteasome activation in PC12-SOD1(G93A) cells. |
Affinity probe pull-down, LC-MS/MS proteomics, competitive displacement with inhibitors, fluorogenic proteasome substrate assay |
ACS chemical neuroscience |
Medium |
25001311
|
| 2021 |
Unassembled PSMC4 forms a complex with PSMC5 and the assembly chaperone PAAF1 (PSMC4-PSMC5-PAAF1 complex) as an intermediate during proteasome base assembly. HERC1 ubiquitin ligase recognizes this unassembled intermediate via PAAF1 (which only dissociates after complete assembly) and targets PSMC5 for degradation; a neurodegeneration-causing missense mutant of HERC1 is impaired in recognizing the PSMC5-PAAF1 complex. |
Co-immunoprecipitation, mass spectrometry, ubiquitination assays, HERC1 mutant analysis in mammalian cells |
Science (New York, N.Y.) |
High |
34446601
|
| 2018 |
PSMC4 is enriched >10-fold in membrane-penetrating cell extensions compared to cell bodies in 3T3 fibroblasts. siRNA knockdown of PSMC4 reduces formation of cell extensions (~42%), collagen compaction (~1.5-fold), and pericellular collagen degradation (~1.7-fold). Recruitment of PSMC4 to extensions depends on Smad3 and ROCK-II signaling pathways. |
Tandem mass tagged mass spectrometry, immunostaining, immunoblotting, siRNA knockdown, collagen gel compaction assay, pathway inhibitor experiments |
Experimental cell research |
Medium |
29476834
|
| 2023 |
PSMC4 promotes prostate carcinoma cell proliferation, cell cycle progression, and migration through regulation of CBX3 levels and downstream EGFR-PI3K-AKT-mTOR signaling. PSMC4 knockdown reduces CBX3 and EGFR levels and inhibits PI3K-AKT-mTOR; CBX3 overexpression rescues EGFR levels. PSMC4 and CBX3 interact as shown by co-IP. |
siRNA knockdown, co-immunoprecipitation, RNA-seq, Western blotting, xenograft tumor model, cell proliferation/apoptosis/migration assays |
Journal of cellular and molecular medicine |
Medium |
37436074
|
| 2009 |
PSMC4 (PSMC4/Rpt3) is present on the sperm acrosomal surface as part of the 19S proteasome complex. Depletion of sperm-surface ATP by apyrase altered the band pattern of PSMC4 (and PSMC1) in Western blotting, suggesting that extracellular ATP is required for integrity of the sperm 19S proteasomal complex and sperm-zona pellucida interactions during fertilization. |
Western blotting, ATP depletion with apyrase, in vitro fertilization assay, luminescence ATP assay |
Systems biology in reproductive medicine |
Low |
19462288
|