Ask about this productRelated genes to: PSMF1 antibody
- Gene:
- PSMF1 NIH gene
- Name:
- proteasome inhibitor subunit 1
- Previous symbol:
- -
- Synonyms:
- PI31
- Chromosome:
- 20p13
- Locus Type:
- gene with protein product
- Date approved:
- 1999-04-15
- Date modifiied:
- 2015-08-12
Related products to: PSMF1 antibody
Related articles to: PSMF1 antibody
- FBXO7 and PI31 variants are linked to rare Parkinsonian syndromes, implicating their dysfunction in neurodegeneration. We define how both engage each other and regulate the proteasome 20S core particle (CP). In cells, each can associate independently with the proteasome, with multiple domains in FBXO7 contributing. Utilizing cryo-EM we visualized how FBXO7's C-terminal domain engages multiple subunits within the CP interior, blocking the β5 peptidase activity. In contrast, we visualized PI31 engagement of all three catalytic sites within the 20S CP, revealing the previously unknown structural basis for β1 inhibition. Furthermore, we establish how disease-associated variants impact both FBXO7 and PI31 function, including disruption of proteasome inhibition and SKP1-FBXO7-PI31 complex assembly. These results establish an unexpected function for FBXO7, providing a mechanistic basis for investigation of its role in proteasome regulation in Parkinson's disease. - Source: PubMed
Publication date: 2026/06/04
Adolf FrankGoodall Ellen ASingh Ekampreetvon Gronau SusannePerez Erignacio FerminFung DarleneMüller BenediktPaulo Joao AHanna JohnHarper J WadeSchulman Brenda A - Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here we identify PSMF1 as a gene implicated in parkinsonism and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD to perinatal lethality with neurological manifestations across 18 pedigrees with 25 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/hPI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants may affect proteasomal abundance and assembly, and are associated with alterations of mitochondrial membrane potential, respiration, dynamics and mitophagy in patient-derived fibroblasts. Furthermore, Drosophila and mouse models of PI31 loss of function exhibit age-dependent motor impairment, as well as brain-wide mitochondrial membrane depolarization and dopaminergic neurodegeneration in aged flies, and diffuse gliosis in mice. Collectively, our findings unequivocally link defective PSMF1/hPI31 to early-onset parkinsonism and neurodegeneration, and suggest proteasomal and mitochondrial dysfunction as pathogenic contributors. - Source: PubMed
Publication date: 2026/04/15
Magrinelli FrancescaTesson ChristelleAngelova Plamena RRodriguez Jose AScardamaglia AnnaritaO'Callaghan BenjaminLowe Simon ASalazar-Villacorta AinaraChung Brian Hon-YinJaconelli MatthewVona BarbaraEsteras NoemiMammana AngelaShimazu JunkoKwong Anna Ka-YeeCourtin ThomasAlavi ShahryarMaroofian RezaNirujogi RajaSeverino MariasavinaMonfrini EdoardoRocca ClarissaLewis Patrick AEfthymiou StephanieBuchert RebeccaSofan LindaLis PawelPinon ChloéBreedveld Guido JChui Martin Man-ChunMurphy DavidPitz VanessaMakarious Mary BBaiardi SimoneVolin MarinaCassar MarleneHassan Bassem AIftikhar SanaBauer PeterTinazzi MicheleSvetel MarinaSamanci BediaHanağası Haşmet ABilgiç BasarCavallieri FrancescoSantangelo MarioObeso José AKurtis Monica MCogan GuillaumeKiziltan GüneşGül-Demirkale TuğçeTireli HülyaYüksel Gülbün AYalçın-Cakmakli GülElibol BülentBarišić NinaNg Earny Wei-SenFan Sze-ShingHershkovitz TovaWeiss KarinAlvi Javeria RazaSultan TipuAlkhawaja Issam AzmiFroukh TawfiqAlrukban Hadeel Abdollah EAnjum Muhammad NadeemSaeed AnjumCheema Huma ArshadFauth ChristineSchatz Ulrich AZöggeler ThomasZech MichaelStals KarenVarghese VinodGandhi SoniaBlauwendraat CornelisHardy John ADi Fonzo AlessioBonifati VincenzoHaack Tobias BBertoli-Avella Aida MLesage SuzanneBaşak Ayşe NazlıSteinfeld RobertParchi PieroJepson James E CAlessi Dario R Brice AlexisSteller HermannAbramov Andrey YBhatia Kailash PHoulden Henry - Early-onset Parkinson's disease (EOPD) is usually defined as Parkinson's disease (PD) occurring before the age of 40-50 years. Unlike late-onset PD, EOPD is often due to pathogenic mutations in autosomal recessive genes. Two phenotypes can be distinguished: typical EOPD, which progresses slowly (PRKN, PINK1 and DJ-1), and atypical PD, often associated with additional symptoms (ATP13A2, FBXO7, DNAJC6, VPS13C, SYNJ1, PLA2G6). In this review, we will highlight recent advances and remaining challenges. The frequency of causal genetic mutations and the genotype-phenotype landscape of PRKN-associated PD has been refined. Long-read sequencing has solved several undiagnosed cases with a single PRKN mutation. Five new genes have been reported to contribute to EOPD associated with various neurological signs (PTPA, DAGLB, PSMF1, EPG5, SGIP1). Small molecules targeting PRKN dysfunctions are expected to enter clinical trials in the coming years, paving the way for targeted therapies in EOPD. - Source: PubMed
Publication date: 2025/11/17
Cogan GuillaumeLesage SuzanneBrice Alexis - Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. This research aims to find real hub genes for prognostic biomarkers of TNBC therapy. The GEO datasets GSE27447 and GSE233242 were analyzed using R package limma to explore DEGs. The PPI was generated using the STRING database. Cytoscape software plug-ins were used to screen the hub genes. Using the DAVID database, GO functional enrichment and KEGG pathway enrichment analysis were performed. Different online expression databases were employed to investigate the functions of real hub genes in tumor driving, diagnosis, and prognosis in TNBC patients with various clinicopathologic characteristics. A total of one hundred DEGs were identified between both datasets. The seven hub genes were identified after the topological parameter analysis of the PPI network. The KEGG pathway and GO analysis suggest that four genes (PSMB1, PSMC1, PSMF1, and PSMD8) are highly enriched in proteasome and were finally considered as real hub genes. Additionally, the expression analysis demonstrated that hub genes were notably up-regulated in TNBC patients compared to controls. Furthermore, correlational analyses revealed the positive and negative correlations among the expression of the real hub genes and various ancillary data, including tumor purity, promoter methylation status, overall survival (OS), genetic alterations, infiltration of CD8+ T and CD4+ immune cells, and a few more, across TNBC samples. Finally, our analysis identified a couple of significant chemotherapeutic drugs, miRNAs and transcription factors (TFS) with intriguing curative potential. In conclusion, we identified four real hub genes as novel biomarkers to overcome heterogenetic-particular challenges in diagnosis, prognosis, and therapy for TNBC patients. - Source: PubMed
Publication date: 2024/10/15
Ali FaisalIqbal AzharAzhar IqraQayyum AdibaHassan Syed AliHasan Md Sakib AlJawi MotasimHassan Hesham MAl-Emam AhmedSajid Muhammad - Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify as a novel gene implicated in parkinsonism and childhood neurodegeneration. We find that biallelic missense and loss-of-function variants co-segregate with phenotypes from early-onset PD to perinatal lethality with neurological manifestations across 17 pedigrees with 24 affected subjects, showing clear genotype-phenotype correlation. encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that variants impair mitochondrial membrane potential, dynamics and mitophagy, and may affect proteasomal abundance and assembly in patient-derived fibroblasts. Furthermore, and mouse models of loss of function exhibit age-dependent motor impairment, as well as brain-wide mitochondrial membrane depolarization and dopaminergic neurodegeneration in aged flies, and diffuse gliosis in mice. Collectively, our findings unequivocally link defective PSMF1 to early-onset parkinsonism and neurodegeneration, and suggest proteasomal and mitochondrial dysfunction as mechanistic contributors. - Source: PubMed
Publication date: 2025/07/21
Magrinelli FrancescaTesson ChristelleAngelova Plamena RRodriguez Jose AScardamaglia AnnaritaO'Callaghan BenjaminLowe Simon ASalazar-Villacorta AinaraChung Brian Hon-YinJaconelli MatthewVona BarbaraEsteras NoemiMammana AngelaShimazu JunkoKwong Anna Ka-YeeCourtin ThomasAlavi ShahryarMaroofian RezaNirujogi RajaSeverino MariasavinaMonfrini EdoardoRocca ClarissaLewis Patrick AEfthymiou StephanieBuchert RebeccaSofan LindaLis PawelPinon ChloéBreedveld Guido JChui Martin Man-ChunMurphy DavidPitz VanessaMakarious Mary BBaiardi SimoneVolin MarinaCassar MarleneHassan Bassem AIftikhar SanaBauer PeterTinazzi MicheleSvetel MarinaSamanci BediaHanağası Haşmet ABilgiç BasarCavallieri FrancescoSantangelo MarioObeso José AKurtis Monica MCogan GuillaumeKiziltan GüneşGül-Demirkale TuğçeTireli HülyaYüksel Gülbün AYalçın-Cakmakli GülElibol BülentBarišić NinaNg Earny Wei-SenFan Sze-ShingHershkovitz TovaWeiss KarinAlvi Javeria RazaSultan TipuAlkhawaja Issam AzmiFroukh TawfiqAlrukban Hadeel Abdollah EFauth ChristineSchatz Ulrich AZöggeler ThomasZech MichaelStals KarenVarghese VinodGandhi SoniaBlauwendraat CornelisHardy John ADi Fonzo AlessioBonifati VincenzoHaack Tobias BBertoli-Avella Aida MLesage SuzanneBaşak Ayşe NazlıSteinfeld RobertParchi PieroJepson James E CAlessi Dario R Brice AlexisSteller HermannAbramov Andrey YBhatia Kailash PHoulden Henry