Ask about this productRelated genes to: PSMD14 antibody
- Gene:
- PSMD14 NIH gene
- Name:
- proteasome 26S subunit, non-ATPase 14
- Previous symbol:
- -
- Synonyms:
- POH1, pad1, Rpn11
- Chromosome:
- 2q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-03-17
- Date modifiied:
- 2016-10-05
Related products to: PSMD14 antibody
Related articles to: PSMD14 antibody
- - Source: PubMed
Publication date: 2026/04/14
Wen ShichaoLiu YuhanLiu QiSu LiqianWang YuhuaMa YiqiuWang Jingxuan - Nutrient competition between tumor and immune cells is a hallmark of the glioblastoma (GBM) microenvironment, yet the mechanisms underlying amino acid metabolic reprogramming and immune evasion remain incompletely understood. Here, we demonstrate that GBM cells outcompete NK cells for branched-chain amino acid (BCAA), leading to BCAA depletion, suppression of NK and CD8 T cell cytotoxicity, and immune escape. Mechanistically, we identify a positive feedback circuit involving PSMD14, BCKDK, and IGF2BP3 that stabilizes BCKDK post-translationally and promotes SLC7A5/SLC7A8-mediated BCAA uptake by GBM cells. PSMD14 directly interacts with and deubiquitinates BCKDK, antagonizing TRIM21-mediated proteasomal degradation. This metabolic remodeling disrupts NK cell signaling and function, as BCAA deprivation impairs PI3K/Akt and cGAS-STING pathways and disrupts mitochondrial integrity. Preclinical models reveal that pharmacologic inhibition of PSMD14 by O-phenanthroline (OPA) or PSMD14 knockdown restores immune cell infiltration, enhances CAR-NK cytotoxicity, and synergizes with immunotherapy to suppress GBM growth. Clinical analysis further establishes that elevated PSMD14 and BCKDK expression in GBM correlates with decreased CD8 T and NK cell infiltration and poorer patient survival. These findings highlight the PSMD14-BCKDK axis as a central regulator of tumor metabolic adaptation and immune suppression, and support PSMD14 inhibition-alone or in combination with CAR-NK therapy-as a promising strategy for precision immunometabolic intervention in GBM. - Source: PubMed
Publication date: 2026/03/25
Yu ShaojieWang MinjieJiang ChengLi XudongWang XuanCheng QihongGong ZihanZhao ZhenHe JieXiang WeiLi JunjunJiang Xiaobing - Targeting ferroptosis is a promising treatment strategy for intrahepatic cholangiocarcinoma (ICC) given the limited number of currently available therapeutic drugs. However, the heterogeneity of tumor cells and their resistance to ferroptosis pose difficulties in the implementation of this strategy. Here, we constructed a novel ferroptosis resistance score (FRS) to quantitatively assess the ferroptosis resistance status of ICC samples. Next, we found that glycolysis is closely associated with the FRS and verified that L-lactate drives ferroptosis resistance via PSMD14 in vitro and in vivo. Mechanistically, L-lactate promoted the K100 lactylation of PSMD14 to delay proteasome-mediated degradation. PSMD14 subsequently interacted with ENO1 to decrease ENO1 K63-linked ubiquitination and inhibited lysosome-mediated ENO1 degradation. Importantly, targeting PSMD14 inhibited L-lactate production and ferroptosis resistance through ENO1 and significantly increased the efficacy of anti-PD-1 treatment. Furthermore, PSMD14 and ENO1 were highly expressed in tumor tissues and closely associated with a poor ICC prognosis. Overall, our study reveals the importance of the L-lactate/PSMD14/ENO1 axis in regulating ferroptosis resistance in ICC, suggesting a novel therapeutic target and strategy for treating this disease. - Source: PubMed
Publication date: 2026/03/03
Cai DongZhong Guo-ChaoZhao ZhiboChen MenglinTao QingDai XinJia DegongCheng LveWu ZhenruLi ShengweiGong JianpingGong Junhua - Triple-negative breast cancer (TNBC), particularly the androgen receptor-low (AR-low) subtype, is one of the most aggressive and hard-to-treat forms of BC, characterized by a high index of proliferation, chromosomal instability (CIN), and high prevalence of TP53 mutations. These features fuel therapy resistance, metastases, and poor clinical outcomes. An integrated framework describing the dysregulated molecular networks that support the pathobiology of AR-low TNBC is lacking. Multiple published studies in breast cancer have previously proposed mechanistic links between TP53 loss, AR-low states, and heightened FOXM1-driven G2/M transcriptional programs, potentially via deregulation of E2F activity, chromatin-associated co-regulators (e.g., ATAD2), and disruption of repressive networks involving p53-p21-DREAM and SPDEF. Additional reports suggest that FOXM1-associated circuitry may be reinforced by chromatin regulators such as WDR5 and by mitotic/spindle factors such as ASPM, including through feedback interactions and condensate-associated transcriptional organization. We previously showed that FOXM1, a master regulator transcription factor, is upregulated and is a biomarker of poor prognosis in AR-low TNBC. In this study, we filtered a set of "TNBC core genes" known to promote transcriptional chaos downstream of FoxM1. We identified a set of 15 cell cycle regulators-including mitotic kinesin motors (KIF14, KIF11, KIF4A, KIF2C, and KIF20A), centromeric proteins (CENPA, CENPO, CENPL, CENPF, and OIP5), and regulators of proteolysis (UBE2C, UBE2S, UBE2T, PSMD14, and TUBA1B). These 15 genes, which were ranked highly among genes overexpressed in TNBC featured prominently in gene signatures of chromosomal instability and were also overexpressed among AR-low TNBCs and TP53-mutant breast tumors. We show that expression of each of these 15 genes correlates positively with proliferation markers (Ki67, PCNA, and MCM2) in TNBC, and that the overexpression of this gene set is associated with shorter relapse-free survival and distinct immune/stromal infiltration patterns. In light of prior work, our findings point to a FOXM1-associated 15-gene signature enriched in AR-low TNBC and associated with the high-proliferation and high-CIN phenotypes of this clinically challenging tumor type. This 15-gene set represents an actionable vulnerability with therapeutic potential for AR-low TNBC and provides a framework for rethinking how to manage highly proliferative, genomically unstable BCs. - Source: PubMed
Publication date: 2026/02/14
Rida PadmashreeAndreae RaphaelBikhazi NoahJackson BeneciaWang IvanJinna Nikita - Choroidal neovascularization (CNV) is a leading cause of central vision impairment with limited treatment options. Ethyl ferulate is a natural compound with antioxidant and anti-angiogenic properties; however, its application for treating CNV and the underlying mechanisms remain largely unexplored. - Source: PubMed
Publication date: 2026/01/30
Xue RongDong Yi-ChenWang XiaLiang Shen-ZhiFan Xia-LianWan Guang-Ming