Affinage

PSMD2

26S proteasome non-ATPase regulatory subunit 2 · UniProt Q13200

Round 2 corrected
Length
908 aa
Mass
100.2 kDa
Annotated
2026-04-28
130 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMD2 (Rpn1) is a non-ATPase subunit of the 19S proteasome regulatory particle that serves as a multivalent ubiquitin-receptor and substrate-docking platform essential for proteasomal proteolysis. Its toroid domain contains two ubiquitin-binding sites: T1, which recognizes K48-linked polyubiquitin chains and UBL domains of substrate-shuttling factors (Rad23, Dsk2, Ubiquilin), and T2, which anchors the deubiquitinase Ubp6, while its LRR-like domain independently docks UBL-domain shuttles (PMID:12198498, PMID:26912900, PMID:28330605). PIM1/2/3-mediated phosphorylation of Ser361 promotes the earliest step of 19S base assembly (Rpn1–Rpt2 precursor formation), with the proteasome-resident phosphatase UBLCP1 providing reversible control; loss of this phosphorylation impairs proteasome activity, cell proliferation, and mitochondrial integrity (PMID:31843888). PSMD2 depletion reduces proteasome activity and triggers apoptosis associated with altered AKT/p38/p21 signaling and decreased lipid droplet accumulation (PMID:21465578, PMID:31703613).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2002 High

    Identifying the proteasomal receptor for UBL-domain shuttle factors resolved how ubiquitinated substrates are delivered to the 26S proteasome, establishing Rpn1 (PSMD2) and its LRR-like domain as the primary docking site for Rad23 and Dsk2.

    Evidence Co-immunoprecipitation, direct binding assays with recombinant proteins, and competition experiments in yeast

    PMID:12198498

    Open questions at the time
    • Structural basis of the LRR-like domain–UBL interaction was not determined
    • Whether additional ubiquitin-binding sites existed on Rpn1 was unknown
  2. 2009 High

    Biochemical reconstitution of 19S subcomplexes positioned Rpn1 among the base subunits that collectively bind ubiquitinated substrates and couple docking to unfolding and translocation, clarifying Rpn1's role within the broader regulatory particle architecture.

    Evidence Synthesis of biochemical reconstitution and structural studies across multiple labs

    PMID:19489727

    Open questions at the time
    • Precise ubiquitin-binding surfaces on Rpn1 were not mapped
    • Mechanism of coordination between Rpn1, Rpn10, and Rpn13 was unresolved
  3. 2012 Medium

    Demonstrating that the ubiquitin-like modifier FAT10 and its accelerator NUB1L dock at Rpn1 extended the receptor function of PSMD2 beyond canonical ubiquitin to other UBL modifier systems.

    Evidence Co-IP, yeast complementation, siRNA knockdown, and domain mapping

    PMID:22434192

    Open questions at the time
    • Which Rpn1 surface binds NUB1L was not defined
    • Relative contribution of Rpn1 versus Rpn10 to FAT10-conjugate degradation was not quantified
  4. 2016 High

    Crystal structures of the Rpn1 toroid domain with monoubiquitin and K48-linked diubiquitin revealed two adjacent binding sites (T1 and T2), establishing Rpn1 as the sixth proteasomal ubiquitin receptor and showing how T1 preferentially engages K48-linked chains while T2 anchors the deubiquitinase Ubp6.

    Evidence X-ray crystallography, mutagenesis, genetic complementation, and in vitro binding in yeast

    PMID:26912900

    Open questions at the time
    • How T1 and T2 coordinate temporally with Rpn10/Rpn13 during substrate processing was not resolved
    • Human PSMD2 crystal structure was not reported
  5. 2017 High

    Photoactivatable ubiquitin crosslinking orthogonally confirmed Rpn1 as a bona fide ubiquitin-associating subunit in intact proteasomes, validating prior structural findings with an independent chemical biology approach.

    Evidence Synthetic photoactivatable ubiquitin probes (UbPT) with mass spectrometry

    PMID:28330605

    Open questions at the time
    • Crosslinking did not resolve stoichiometry of ubiquitin occupancy across Rpn1, Rpn10, and Rpn13 simultaneously
  6. 2019 High

    Identifying PIM kinases as the writers and UBLCP1 as the eraser of Rpn1 Ser361 phosphorylation revealed the first regulatory switch controlling 19S base assembly, showing that phospho-S361 promotes the Rpn1–Rpt2 precursor complex and that its loss impairs proteasome function, proliferation, and mitochondrial health.

    Evidence CRISPR editing of Ser361, kinome screen, genetic code expansion for site-specific phosphorylation, quantitative mass spectrometry, and assembly assays

    PMID:31843888

    Open questions at the time
    • Whether Ser361 phosphorylation status changes during stress or cell-cycle transitions was not examined
    • Structural mechanism by which phospho-S361 favors Rpt2 binding is unknown
  7. 2011 Medium

    PSMD2 knockdown in lung cancer cells linked proteasome function to AKT/p38/p21 signaling and cell survival, providing the first evidence that PSMD2 loss triggers apoptosis through specific signaling pathways rather than generic proteotoxicity alone.

    Evidence siRNA knockdown, proteasome activity assays, western blot for pAKT/p38/p21, and apoptosis assays in human lung cancer lines

    PMID:21465578

    Open questions at the time
    • Whether signaling changes are direct or secondary to proteasome impairment was not distinguished
    • Not replicated in non-cancer cell types
  8. 2019 Medium

    Extending the cancer-cell phenotype, PSMD2 and PSMD1 knockdown in hepatoma cells reduced lipid droplet accumulation and de novo lipogenesis gene expression via p38-JNK and AKT pathways, linking proteasomal subunit levels to metabolic reprogramming.

    Evidence siRNA knockdown, lipid droplet staining, and MAPK/AKT pathway western blots in HepG2 cells

    PMID:31703613

    Open questions at the time
    • Whether lipid metabolism effects are PSMD2-specific or reflect general proteasome inhibition is unclear
    • In vivo metabolic phenotype not assessed
  9. 2018 Medium

    Direct interaction between ATG16 and PSMD2 in Dictyostelium connected the proteasome to autophagy machinery, showing ATG16 is required for PSMD2 enrichment in autophagosomes/autolysosomes.

    Evidence Yeast two-hybrid, Co-IP, fluorescence co-localization, and deletion mapping in Dictyostelium

    PMID:30269947

    Open questions at the time
    • Conservation of ATG16–PSMD2 interaction in mammalian cells was not demonstrated
    • Functional consequence for proteasome activity within autolysosomes is unknown
  10. 2023 Medium

    Two studies expanded PSMD2's interactome in cancer contexts: RACK1 competes with β-catenin for PSMD2 binding to protect β-catenin from degradation and activate WNT signaling, while DNAJA4 recruits PSMD2 for substrate-specific MYH9 degradation, illustrating PSMD2 as a regulatable access point for proteasomal substrates.

    Evidence Co-IP, competitive binding assays, siRNA knockdown, and in vivo tumor models in breast and nasopharyngeal carcinoma cells

    PMID:37848434 PMID:37875476

    Open questions at the time
    • RACK1–PSMD2 interaction surface is unmapped
    • DNAJA4–PSMD2 link relies on single Co-IP without reciprocal validation
    • Whether these interactions occur at the intact 26S proteasome or free PSMD2 is not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of human PSMD2's T1/T2 sites, how Ser361 phosphorylation dynamics integrate with cellular stress responses, and whether PSMD2 functions outside the 26S holoenzyme context (e.g., in autophagy-linked roles or as a free subunit with signaling activity).
  • No human PSMD2 crystal structure exists
  • In vivo genetic models (knockout mouse) have not been reported
  • Relative contributions of T1 versus Rpn10/Rpn13 to substrate degradation in intact cells are unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 2
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-9612973 Autophagy 1
Partners
ASPNDNAJA4PIM1PSMD1RACK1RAD23BUBLCP1UBQLN1
Complex memberships
19S regulatory particle26S proteasome

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Yeast Rpn1 (ortholog of human PSMD2), a subunit of the 19S proteasome base, directly binds the ubiquitin-like (UBL) domains of Rad23 and Dsk2 through its leucine-rich-repeat-like (LRR-like) domain. Rad23 and Dsk2 compete for the same Rpn1 binding site, identifying Rpn1 as the primary docking site for UBL-domain substrate-shuttling factors at the proteasome. Co-immunoprecipitation, direct binding assays with recombinant proteins, yeast genetic analysis, competition binding experiments Nature cell biology High 12198498
2009 Recognition and processing of ubiquitin-protein conjugates by the proteasome involves Rpn1 (PSMD2) as part of the 19S regulatory particle base, where it participates in substrate docking alongside the ATPase ring. The 19S regulatory particle's non-ATPase subunits including Rpn1 are essential for binding ubiquitinated substrates and initiating their unfolding and translocation into the 20S core. Biochemical reconstitution of proteasome subcomplexes, structural and functional analysis reviewed across multiple studies Annual review of biochemistry High 19489727
2012 FAT10 (a ubiquitin-like modifier) and its accelerator NUB1L both interact with the 26S proteasome via Rpn1 (PSMD2/S2). NUB1L can bind to both Rpn10 and Rpn1, and depletion of Rpn10 causes accumulation of FAT10-conjugates, while Rpn1 serves as an additional docking site for NUB1L to initiate FAT10-mediated proteasomal proteolysis. Co-immunoprecipitation, yeast complementation assays, siRNA knockdown, binding domain mapping Nature communications Medium 22434192
2016 Rpn1 (PSMD2 ortholog) contains two adjacent ubiquitin-binding sites within its toroid domain: site T1, which recognizes monoubiquitin, K48-linked diubiquitin, and UBL domains of substrate-shuttling factors (Rad23, Dsk2, Ubiquilin) with preference for K48-linked chains; and site T2, which binds the UBL domain of the deubiquitinase Ubp6 to facilitate ubiquitin chain disassembly. Crystal structures of T1 with monoubiquitin or K48 diubiquitin reveal three neighboring outer helices engaging two ubiquitin moieties. Rpn1 constitutes the sixth proteasomal ubiquitin receptor and its T1 site defines a distinct substrate-binding pathway. X-ray crystallography of T1–ubiquitin complexes, genetic complementation, in vitro binding assays, biochemical ubiquitin receptor identification by mutagenesis Science (New York, N.Y.) High 26912900
2017 Photoactivatable crosslinking with ubiquitin variants (UbPT) confirmed Rpn1 (PSMD2) as a third proteasome ubiquitin-associating subunit (alongside Rpn10 and Rpn13), demonstrating that Rpn1 coordinates docking of substrate shuttles, substrate unloading, and anchoring of polyubiquitin conjugates at the proteasome. Synthetic photoactivatable ubiquitin crosslinking reagents (UbPT), mass spectrometry, proteasome biochemistry Cell chemical biology High 28330605
2011 siRNA-mediated knockdown of PSMD2 in lung cancer cell lines decreased proteasome activity and induced growth inhibition and apoptosis. These effects were associated with changes in the balance between phosphorylated AKT and p38, as well as induction of p21, placing PSMD2 upstream of AKT/p38 signaling in cancer cell survival. siRNA knockdown, proteasome activity assays, western blot for pAKT, p38, p21, cell viability and apoptosis assays Molecular carcinogenesis Medium 21465578
2019 Reversible phosphorylation of Rpn1 (PSMD2 ortholog) at Ser361 regulates 26S proteasome assembly and function. Loss of Ser361 phosphorylation reduces proteasome activity, impairs cell proliferation, and causes oxidative stress and mitochondrial dysfunction. PIM1/2/3 kinases catalyze this phosphorylation, while the proteasome-resident phosphatase UBLCP1 reverses it. Mechanistically, phospho-S361 Rpn1 more readily forms a precursor complex with Rpt2, representing one of the first steps of 19S base assembly. CRISPR/Cas9 gene editing of Ser361, quantitative mass spectrometry, kinome screen, genetic code expansion for site-specific phosphorylation, 26S proteasome assembly assays Proceedings of the National Academy of Sciences of the United States of America High 31843888
2019 PSMD1 and PSMD2 (19S regulatory particle subunits) promote HepG2 cell proliferation by facilitating cellular lipid droplet accumulation. Knockdown of PSMD1 and/or PSMD2 decreases lipid droplet formation and reduces expression of de novo lipid synthesis genes via p38-JNK and AKT signaling pathways. siRNA knockdown, lipid droplet staining, western blot for lipid synthesis regulators, AKT and MAPK pathway analysis BMC molecular biology Medium 31703613
2018 PSMD1 and PSMD2 (components of the 19S proteasome regulatory particle) directly interact with Dictyostelium ATG16, a core autophagosomal protein. Deletion analysis showed the N-terminal half of ATG16 interacted with PSMD1 only, while the C-terminal half interacted with both PSMD1 and PSMD2. ATG16 is required for enrichment of PSMD2 in autophagosomes/autolysosomes, establishing that ATG16 links autophagy to the ubiquitin-proteasome system via direct interaction with 19S subunits. Yeast two-hybrid, co-immunoprecipitation, fluorescence co-localization, deletion mapping, lysotracker labeling, proteolytic cleavage assay European journal of cell biology Medium 30269947
2019 Asporin (ASPN) promotes gastric cancer cell proliferation by directly interacting with PSMD2. Co-immunoprecipitation showed ASPN and PSMD2 form a complex in gastric cancer cells. Knockdown of ASPN increased expression of DUSP7, WIP1, and PTEN and reduced phosphorylation of ERK, P38, and AKT; these changes were counteracted by PSMD2 knockdown, placing PSMD2 downstream of ASPN in a proliferative signaling cascade. Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown of ASPN and PSMD2, western blot for DUSP7/WIP1/PTEN/ERK/p38/AKT Frontiers in bioscience (Landmark edition) Low 31136974
2023 RACK1 competes with β-catenin for binding to PSMD2 (a key proteasome component). RACK1 binds PSMD2 and prevents ubiquitinated β-catenin from accessing PSMD2, thereby protecting β-catenin from proteasomal degradation and activating canonical WNT signaling in breast cancer cells. This identifies PSMD2 as a novel binding partner for both RACK1 and β-catenin at the proteasome. Co-immunoprecipitation, competitive binding assays, siRNA knockdown, in vivo tumor growth assays, western blot Cell death & disease Medium 37848434
2023 DNAJA4 facilitates MYH9 protein degradation via the ubiquitin-proteasome pathway by recruiting PSMD2. Loss of DNAJA4 in nasopharyngeal carcinoma cells impairs MYH9 degradation and promotes EMT and metastasis. This places PSMD2 as the proteasomal docking factor recruited by DNAJA4 for substrate-specific degradation. Co-immunoprecipitation, overexpression and knockdown experiments, in vivo metastasis assays, ubiquitin-proteasome pathway analysis Cell death & disease Low 37875476

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
1996 Structure and functions of the 20S and 26S proteasomes. Annual review of biochemistry 2108 8811196
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 1924 12167863
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annual review of biochemistry 1398 19489727
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2003 Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 1236 12808466
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2003 DNA deamination mediates innate immunity to retroviral infection. Cell 1150 12809610
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science (New York, N.Y.) 1006 14564014
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2003 The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 912 12808465
2013 Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 870 23503661
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nature medicine 798 14528300
2003 Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 763 12859895
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2003 HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nature medicine 679 14528301
2014 The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis. Journal of cell science 382 25146396
2002 Proteasome subunit Rpn1 binds ubiquitin-like protein domains. Nature cell biology 373 12198498
2017 VCP/p97-Mediated Unfolding as a Principle in Protein Homeostasis and Signaling. Molecular cell 335 29153394
2016 Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome. Science (New York, N.Y.) 251 26912900
2004 Molecular perspectives on p97-VCP: progress in understanding its structure and diverse biological functions. Journal of structural biology 246 15037236
2019 ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97. Molecular cell 151 30979586
2011 Recent advances in p97/VCP/Cdc48 cellular functions. Biochimica et biophysica acta 147 21781992
2016 Structure and function of the AAA+ ATPase p97/Cdc48p. Gene 139 26945625
2010 Expression in aneuploid Drosophila S2 cells. PLoS biology 139 20186269
2012 DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage. Nature structural & molecular biology 122 23042607
1985 Pharmacology of potent and selective S2-serotonergic antagonists. Journal of cardiovascular pharmacology 118 2412048
2008 Insights into adaptor binding to the AAA protein p97. Biochemical Society transactions 117 18208387
2017 The AAA+ ATPase p97, a cellular multitool. The Biochemical journal 115 28819009
2017 Toward an understanding of the Cdc48/p97 ATPase. F1000Research 108 28815021
2005 p97/p47-Mediated biogenesis of Golgi and ER. Journal of biochemistry 93 15749824
2015 Altered cofactor regulation with disease-associated p97/VCP mutations. Proceedings of the National Academy of Sciences of the United States of America 91 25775548
2016 VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break Repair. Molecular cell 87 27716483
2012 Growing sphere of influence: Cdc48/p97 orchestrates ubiquitin-dependent extraction from chromatin. Trends in cell biology 87 22818974
2000 Essential role of NAT1/p97/DAP5 in embryonic differentiation and the retinoic acid pathway. The EMBO journal 87 11032820
2020 TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts. Nature communications 86 32152270
2016 Mutations in the Human AAA+ Chaperone p97 and Related Diseases. Frontiers in molecular biosciences 82 27990419
2015 Inhibitors of the AAA+ chaperone p97. Molecules (Basel, Switzerland) 78 25685910
2016 Ring of Change: CDC48/p97 Drives Protein Dynamics at Chromatin. Frontiers in genetics 76 27200082
2008 AAA ATPase p97/VCP: cellular functions, disease and therapeutic potential. Journal of cellular and molecular medicine 76 18798739
2012 Expanding into new markets--VCP/p97 in endocytosis and autophagy. Journal of structural biology 74 22450227
1984 Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain. Psychiatry research 74 6239298
2017 p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates. Proceedings of the National Academy of Sciences of the United States of America 73 28320958
2012 FAT10 and NUB1L bind to the VWA domain of Rpn10 and Rpn1 to enable proteasome-mediated proteolysis. Nature communications 73 22434192
2021 Mechanistic insight into substrate processing and allosteric inhibition of human p97. Nature structural & molecular biology 71 34262183
2011 Regulation of p97 in the ubiquitin-proteasome system by the UBX protein-family. Biochimica et biophysica acta 68 21963883
2003 DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP. Molecular biology of the cell 67 12937274
2003 NSF and p97/VCP: similar at first, different at last. FEBS letters 67 14630332
1998 Identification of the cilium binding epitope of the Mycoplasma hyopneumoniae P97 adhesin. Infection and immunity 66 9746576
2023 Inhibitors of the ATPase p97/VCP: From basic research to clinical applications. Cell chemical biology 62 36640759
2010 The complexities of p97 function in health and disease. Molecular bioSystems 61 21152665
2011 Cdc48/p97, a key actor in the interplay between autophagy and ubiquitin/proteasome catabolic pathways. Biochimica et biophysica acta 60 21807033
2009 New ATPase regulators--p97 goes to the PUB. The international journal of biochemistry & cell biology 58 19497384
1997 Cloning and functional analysis of the P97 swine cilium adhesin gene of Mycoplasma hyopneumoniae. Journal of bacteriology 58 9023217
2019 Multisystem Proteinopathy Mutations in VCP/p97 Increase NPLOC4·UFD1L Binding and Substrate Processing. Structure (London, England : 1993) 57 31623962
2013 P97/CDC-48: proteostasis control in tumor cell biology. Cancer letters 57 23726843
2011 Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas. Molecular carcinogenesis 51 21465578
2016 Targeting p97 to Disrupt Protein Homeostasis in Cancer. Frontiers in oncology 50 27536557
2011 Development of p97 AAA ATPase inhibitors. Autophagy 49 21606684
2015 A non-canonical role of the p97 complex in RIG-I antiviral signaling. The EMBO journal 47 26471729
2019 Reversible phosphorylation of Rpn1 regulates 26S proteasome assembly and function. Proceedings of the National Academy of Sciences of the United States of America 46 31843888
2012 Roles of p97-associated deubiquitinases in protein quality control at the endoplasmic reticulum. Current protein & peptide science 46 22812527
2007 The melanoma tumor antigen, melanotransferrin (p97): a 25-year hallmark--from iron metabolism to tumorigenesis. Oncogene 46 17452986
2005 Increased expression of valosin-containing protein (p97) is correlated with disease recurrence in follicular thyroid cancer. Annals of surgical oncology 46 16189643
2016 Strategic role of the ubiquitin-dependent segregase p97 (VCP or Cdc48) in DNA replication. Chromosoma 44 27086594
2019 PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism. BMC molecular biology 43 31703613
2013 Create and preserve: proteostasis in development and aging is governed by Cdc48/p97/VCP. Biochimica et biophysica acta 43 23583830
2009 p97/valosin-containing protein (VCP) is highly modulated by phosphorylation and acetylation. Genes to cells : devoted to molecular & cellular mechanisms 43 19335618
2018 Skeletal Muscle-Specific Methyltransferase METTL21C Trimethylates p97 and Regulates Autophagy-Associated Protein Breakdown. Cell reports 41 29719249
2017 Polyubiquitin-Photoactivatable Crosslinking Reagents for Mapping Ubiquitin Interactome Identify Rpn1 as a Proteasome Ubiquitin-Associating Subunit. Cell chemical biology 41 28330605
2011 Altered intracellular localization and valosin-containing protein (p97 VCP) interaction underlie ATP7A-related distal motor neuropathy. Human molecular genetics 41 22210628
2013 The p97-UFD1L-NPL4 protein complex mediates cytokine-induced IκBα proteolysis. Molecular and cellular biology 39 24248593
2007 Mutations in p97/VCP induce unfolding activity. FEBS letters 38 17346713
2019 Asporin promotes cell proliferation via interacting with PSMD2 in gastric cancer. Frontiers in bioscience (Landmark edition) 35 31136974
2009 UBXD1 binds p97 through two independent binding sites. Biochemical and biophysical research communications 35 19174149
2009 Structure and function of the PLAA/Ufd3-p97/Cdc48 complex. The Journal of biological chemistry 34 19887378
2018 Cooperative subunit dynamics modulate p97 function. Proceedings of the National Academy of Sciences of the United States of America 33 30584095
2013 A unique IBMPFD-related P97/VCP mutation with differential binding pattern and subcellular localization. The international journal of biochemistry & cell biology 33 23333620
2021 CUL2LRR1 , TRAIP and p97 control CMG helicase disassembly in the mammalian cell cycle. EMBO reports 32 33590678
2023 Structural basis of ubiquitin-independent PP1 complex disassembly by p97. The EMBO journal 30 37264685
2022 Active conformation of the p97-p47 unfoldase complex. Nature communications 30 35552390
2018 The ATPase VCP/p97 functions as a disaggregase against toxic Huntingtin-exon1 aggregates. FEBS letters 30 30069866
2023 Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine. Frontiers in molecular biosciences 29 36825201
2017 VCP/p97/Cdc48, A Linking of Protein Homeostasis and Cancer Therapy. Current molecular medicine 28 29521227
2016 p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein-Protein Interactions. ACS chemical biology 28 27267671
2003 Association of 3q21q26 syndrome with different RPN1/EVI1 fusion transcripts. Haematologica 28 14607750
2020 Allosteric p97 Inhibitors Can Overcome Resistance to ATP-Competitive p97 Inhibitors for Potential Anticancer Therapy. ChemMedChem 27 32162487
2011 [Novel reference gene RPN1 for normalization of quantitative data in lung and kidney cancer]. Molekuliarnaia biologiia 26 21634111
2014 The p97-FAF1 protein complex reveals a common mode of p97 adaptor binding. The Journal of biological chemistry 25 24619421
2012 SCC-S2 is overexpressed in colon cancers and regulates cell proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 22886548
2022 Cooperative assembly of p97 complexes involved in replication termination. Nature communications 24 36329031
2021 VPS13D interacts with VCP/p97 and negatively regulates endoplasmic reticulum-mitochondria interactions. Molecular biology of the cell 24 34133214
2017 Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes. Frontiers in molecular biosciences 24 28611990
2024 VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy. Autophagy 23 38762759
2022 Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase. eLife 23 35920641
2018 ATG16 mediates the autophagic degradation of the 19S proteasomal subunits PSMD1 and PSMD2. European journal of cell biology 23 30269947
2024 Characterizing ATP processing by the AAA+ protein p97 at the atomic level. Nature chemistry 22 38326645
2023 RACK1 facilitates breast cancer progression by competitively inhibiting the binding of β-catenin to PSMD2 and enhancing the stability of β-catenin. Cell death & disease 22 37848434
2022 K27-linked ubiquitylation promotes p97 substrate processing and is essential for cell proliferation. The EMBO journal 22 35349166
2016 Structure and functions of the chaperone-like p97/CDC48 in plants. Biochimica et biophysica acta. General subjects 22 27717811
2014 Signal-peptide-mediated translocation is regulated by a p97-AIRAPL complex. The Biochemical journal 22 24160817
2021 Structural and Functional Analysis of Disease-Linked p97 ATPase Mutant Complexes. International journal of molecular sciences 21 34360842
2021 Temporal proteomics reveal specific cell cycle oncoprotein downregulation by p97/VCP inhibition. Cell chemical biology 21 34847375
2021 How Viruses Use the VCP/p97 ATPase Molecular Machine. Viruses 20 34578461
2019 Discovery of Irreversible p97 Inhibitors. Journal of medicinal chemistry 20 30830772
2019 Small-Molecule Modulators of the ATPase VCP/p97 Affect Specific p97 Cellular Functions. ACS chemical biology 20 31790201
2016 Selective inhibition of p97 by chlorinated analogues of dehydrocurvularin. Organic & biomolecular chemistry 20 27223265
2021 Targeted substrate loop insertion by VCP/p97 during PP1 complex disassembly. Nature structural & molecular biology 19 34824462
2015 An ALS disease mutation in Cdc48/p97 impairs 20S proteasome binding and proteolytic communication. Protein science : a publication of the Protein Society 19 26134898
2009 The ubiquitin-selective chaperone CDC-48/p97, a new player in DNA replication. Cell cycle (Georgetown, Tex.) 19 19158489
2023 The NRF2-p97-NRF2 negative feedback loop. Redox biology 18 37573837
2020 Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion. International journal of molecular sciences 18 32961852
1999 Phosphorylation of p97(VCP) and p47 in vitro by p34cdc2 kinase. European journal of cell biology 18 10350210
2023 The p97/VCP segregase is essential for arsenic-induced degradation of PML and PML-RARA. The Journal of cell biology 17 36880596
2023 DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation. Cell death & disease 17 37875476
2020 Ribosomal protein S2 interplays with MDM2 to induce p53. Biochemical and biophysical research communications 17 31928715