| 2007 |
PAC4 (PSMG4) was identified as a mammalian proteasome assembly chaperone functioning as part of the PAC3-PAC4 heterodimer pair, acting at early stages of 20S proteasome assembly (alpha-ring formation), analogous to yeast Poc3/Poc4. It works upstream of the half-proteasome maturase UMP1. |
Genetic phenotype screen, yeast and mammalian cell-based functional complementation, identification of functional homologs |
Molecular cell |
High |
17707236
|
| 2008 |
PAC3-PAC4 heterodimer promotes assembly of rings composed of seven alpha subunits of the 20S proteasome core particle, acting prior to beta-subunit incorporation and prior to UMP1-dependent half-proteasome dimerization. |
Biochemical fractionation, assembly intermediate analysis, review/synthesis of experimental data |
Structure (London, England : 1993) |
Medium |
18786393
|
| 2010 |
PAC3-PAC4 heterodimer is implicated in alpha-ring formation during 20S proteasome core particle assembly; PAC3-PAC4 acts upstream of beta-subunit incorporation and UMP1 function. |
Biochemical analysis of assembly intermediates, review of experimental data |
Biochemical Society transactions |
Medium |
20074030
|
| 2017 |
Crystal structure of human PAC4 (PSMG4) determined at 1.90-Å resolution, revealing a hydrophobic surface surrounded by charged residues that is complementary to its binding partner PAC3 and exhibits charge complementarity with proteasomal α4-5 subunits. |
X-ray crystallography at 1.90-Å resolution |
Protein science : a publication of the Protein Society |
High |
28263418
|
| 2018 |
PAC3-PAC4 is required for formation of the core α4-α7 intermediate as the initial step of α-ring assembly. Without PAC3-PAC4, the α4-α7 core intermediate does not form. PAC1-PAC2 then prevents nonproductive dimerization of α-ring assembly intermediates and retains them in the cytoplasm by overriding nuclear localization signals of α-subunits. |
Co-immunoprecipitation, knockdown experiments, subcellular fractionation, overexpression of assembly intermediates |
Genes to cells : devoted to molecular & cellular mechanisms |
High |
30133132
|
| 2019 |
The PAC3-PAC4 heterodimer functions as a molecular matchmaker, stabilizing the α4-α5-α6 subcomplex during α-ring assembly. A 0.96-Å crystal structure of PAC3 homodimer and NMR data revealed loop mobility (residues 51-61) and enabled modeling of the PAC3-4/α4/α5/α6 quintet complex. |
X-ray crystallography (0.96-Å resolution), NMR spectroscopy, 3D structural modeling, biochemical binding assays |
International journal of molecular sciences |
High |
31067643
|
| 2022 |
PAC3-PAC4 is required for selective incorporation of immunoproteasome-specific beta subunits (β1i, β2i) before other beta subunits during immunoproteasome assembly, providing selectivity against constitutive subunits. |
Biochemical assembly intermediate analysis, review of experimental data |
Cells |
Medium |
35563886
|
| 2024 |
Cryo-EM structures of chaperone-bound human 20S proteasome assembly intermediates show that PAC3/PAC4 stabilizes an early α-ring intermediate subcomplex together with PAC1-PAC2. Dissociation of PAC3/PAC4 (along with rearrangement of PAC1 N-terminal tail) triggers the transition to β-ring assembly. Completion of β-ring and half-proteasome dimerization repositions lysine K33 to trigger β pro-peptide cleavage, leading to concerted dissociation of POMP and PAC1/PAC2. |
Cryo-EM of endogenously CRISPR-tagged chaperone-bound complexes, structural analysis of assembly intermediates |
Nature communications |
High |
39294158
|
| 2024 |
Cryo-EM reconstructions of seven recombinant human proteasome subcomplexes visualize PAC4 as part of the chaperone ensemble stabilizing early assembly intermediates; PAC3/PAC4 dissociation is required for progression from α-ring to β-ring assembly. Structural data explain the order of successive subunit additions and how assembly factors rearrange to coordinate proteolytic activation. |
Cryo-EM of recombinant human subcomplexes, structural comparison of intermediates and mature CP |
bioRxiv : the preprint server for biologypreprint |
Medium |
38328185
|
| 2025 |
CRISPR/Cas9 genome-wide knockout screen identified PSMG4 as a gene whose loss confers resistance to colibactin-induced cytotoxicity, suggesting PSMG4 participates in the cellular response pathway to colibactin-mediated DNA damage. (Note: mechanistic validation was performed for PSMD4, not PSMG4, in this study.) |
Genome-wide CRISPR/Cas9 knockout screen with MAGeCK scoring |
mSphere |
Low |
39918307
|
| 2025 |
Caffeine treatment of colorectal adenocarcinoma cells decreased expression of PAC4 (PSMG4) coincident with reduced immunoproteasome content and reduced oxidative stress, suggesting PAC4 expression is linked to immunoproteasome biogenesis in cancer cells. |
qPCR, Western blot, transcriptome analysis, flow cytometry of proteasome subunit expression |
Biochimie |
Low |
40349826
|
| 2026 |
Alternative splicing of Psmg4 pre-mRNA regulated by the SRSF5 splicing factor promotes exon 2 skipping, reducing full-length Psmg4 isoform expression. A tRNA-derived fragment (CHAtRF) directly interacts with SRSF5, blocking its binding to Psmg4 pre-mRNA and thereby promoting exon 2 skipping, which inhibits full-length PSMG4 expression and contributes to pathological cardiac hypertrophy. |
RNA pulldown/interaction assays, alternative splicing reporter assays, cardiac hypertrophy models (AngII-treated mice, hiPSC-CMs), CHAtRF overexpression/knockdown |
Research (Washington, D.C.) |
Medium |
41907183
|