Ask about this productRelated genes to: KPNB1 Blocking Peptide
- Gene:
- KPNB1 NIH gene
- Name:
- karyopherin subunit beta 1
- Previous symbol:
- -
- Synonyms:
- NTF97, IPOB, MGC2155, MGC2156, MGC2157, IMB1, Impnb, IPO1
- Chromosome:
- 17q21.32
- Locus Type:
- gene with protein product
- Date approved:
- 1997-04-21
- Date modifiied:
- 2016-02-01
Related products to: KPNB1 Blocking Peptide
Related articles to: KPNB1 Blocking Peptide
- To define the transcriptional features, spatial distribution, and immune-related properties of an antigen-presenting cancer-associated fibroblast (CAF)-like state in nonsmall cell lung cancer (NSCLC), and to evaluate its relationship with the nuclear factor erythroid 2-related factor 2 (NRF2)-karyopherin subunit beta 1 (KPNB1) axis, multi-omics analyses integrating single-cell RNA sequencing, spatial transcriptomics, and bulk transcriptomic data were performed. Functional validation used primary CAFs from patients with NSCLC, including NRF2 perturbation, KPNB1 knockdown, T-cell co-culture assays, and an orthotopic murine lung cancer model treated with antiprogrammed cell death protein 1 (anti-PD-1)-based combinations. A major histocompatibility complex class II (MHC-II)-associated antigen-presenting CAF-like (apCAF-like) state was identified in NSCLC. It showed increased antigen-presentation-related molecules, limited co-stimulatory molecule expression, and inferred communication involving MHC-II, transforming growth factor-β, and C-X-C motif chemokine ligand pathways. Higher KPNB1 expression was associated with poorer survival, lower immune infiltration, and lower ImmuneScore. In primary CAFs, NRF2 activation increased KPNB1 and reduced class II MHC transactivator, major histocompatibility complex class II DR alpha (HLA-DRA), and MHC-II-related signals, whereas NRF2 inhibition showed the opposite pattern. KPNB1-low CAFs enhanced T-cell activation and cytokine release, and KPNB1 knockdown enriched antigen-presentation-related transcriptional programs. In vivo, inhibition of the NRF2-KPNB1 axis enhanced response to anti-PD-1. NSCLC contains an MHC-II-associated apCAF-like state linked to the NRF2-KPNB1 axis and altered response to PD-1 blockade. - Source: PubMed
Publication date: 2026/06/04
Zheng FeiDeng RuoyingHou RanHong LeiCui YanzhiLiu Yibing - Metabolic reprogramming is a hallmark of lung adenocarcinoma (LUAD) progression and therapeutic resistance. Gasdermin C (GSDMC) is frequently upregulated in patients with LUAD and correlates with poor prognosis. Under nutrient stress or ionizing radiation, phosphorylated STAT3 at Ser727 transcriptionally induces GSDMC, which translocates into the nucleus via the IPO7-KPNB1-NUP93 complex. In the nucleus, GSDMC functions as a scaffold molecule, recruiting NAT10 to mediate histone H3 acetylation and recruiting BAZ1B/SMARCA5 to modulate chromatin remodeling and chromatin accessibility. These changes facilitate CAMKK2-AMPK pathway activation. The GSDMC-CAMKK2-AMPK axis promotes metabolic reprogramming toward glycolysis and fatty acid oxidation, supporting LUAD cell proliferation and survival. Importantly, GSDMC contributes to LUAD radioresistance through the STAT3-GSDMC-CAMKK2-AMPK axis, and targeting any component of this pathway enhances radiotherapy sensitivity in preclinical models. Our findings identify a regulatory role for GSDMC in LUAD progression via metabolic reprogramming and support its potential as a preclinical candidate target to improve radiotherapy response. - Source: PubMed
Publication date: 2026/05/22
Ren DelongLi YunyunLu MingquanJiang WuqiaoXu HaoWu LijunYu K NHan Wei - Anthracycline-induced cardiotoxicity continues to be a significant clinical challenge in oncology, affecting up to 30% of patients who are subjected to sequential chemotherapy regimens and substantially restricting the therapeutic potential of these highly effective anticancer agents. Despite the fact that anthracycline-based chemotherapy has an overall 5-year survival rate of 80%, dose-dependent cardiotoxicity is a rising safety concern which manifests as cardiomyopathy or congestive heart failure. This highlights the need for novel cardioprotective strategies are required as the currently available regimens are insufficiently effective. Anthracycline exposure induces proprotein convertase subtilisin/kexin type 9 (PCSK9) upregulation in cardiomyocytes in a concentration- and time-dependent manner. The nuclear accumulation induces apoptosis through the degradation of karyopherin subunit beta-1 (KPNB1). Elevated PCSK9 levels are linked to pathological remodeling, increased myocardial fibrosis, and a reduced left ventricular ejection fraction. Cardioprotection against Anthracycline-induced cardiotoxicity is primarily achieved through lipid-independent mechanisms, including the suppression of inflammasome-mediated injury, modulation of innate immune signaling, attenuation of myocardial fibrosis, and restoration of mitochondrial homeostasis, which are regulated by PCSK9 inhibition. The inhibition of PCSK9 has been demonstrated in preclinical models to enhance anticancer efficacy by reducing chemoresistance and increasing cardiomyocyte viability by 35-88% during anthracycline/trastuzumab exposure. - Source: PubMed
Publication date: 2026/05/08
Gadelmawla Ahmed FaridAlkuwaiti Mohanad AAlsubaiei Amal AAlSejari Najat YAlharran Abdullah MAbdul-Hafez Hamza AMohamed Ahmed ElmorsyFrishman William HAronow Wilbert S - TMEM106B is a lysosomal membrane protein and major genetic modifier of multiple neurodegenerative diseases, including frontotemporal lobar degeneration, Alzheimer's disease, and amyotrophic lateral sclerosis. Proteolytically generated C-terminal fragments of TMEM106B assemble into amyloid fibrils that accumulate in the brains of individuals with neurodegenerative disease and in cognitively normal aged adults, yet how these fibrils produce neuronal dysfunction has remained unclear. Here, we show that cytosolic and lysosome-directed TMEM106B C-terminal fragments (CTF and gCTF) form detergent-insoluble amyloid aggregates, drive redistribution of endogenous TDP-43 from the nucleus to the cytoplasm, and accelerate neuronal death. Unbiased proximity proteomics identified the inner nuclear membrane LAP1-TorsinA axis as a fragment-specific interactome, and co-immunoprecipitation confirmed a direct physical interaction between gCTF and LAP1 that was not observed with full-length TMEM106B. Fragment expression disrupted Lamin B1 organization, mislocalized the nuclear import machinery KPNB1 and RanGAP1, and impaired importin-dependent nuclear transport in primary cortical neurons. Critically, neurons harboring endogenous TMEM106B fibrillar pathology in aged human frontal cortex exhibited the same phenotypes, namely disrupted Lamin B1 and LAP1 localization and cytoplasmic redistribution of TDP-43, whereas fibril-negative neurons from the same cases and younger control tissue retained intact nuclear envelope organization. These findings define TMEM106B proteinopathy as an upstream driver of nuclear envelope disruption and nucleocytoplasmic transport failure, linking a widespread feature of brain aging to a central mechanism of neurodegeneration. - Source: PubMed
Publication date: 2026/04/27
Tilahun KedamawitParameswaran JananiDudley MylesPun DanielMa FuyingZhang JesseeBold TatianaJiang Jie - As a frequently occurring malignant disorder in women, breast cancer (BC) is closely associated with circular RNAs (circRNAs) in mediating its pathological progression. Accumulating evidence suggests that hsa_circ_0001588 promotes BC via microRNA (miRNA) sponging. - Source: PubMed
Publication date: 2026/04/06
Wu WeiGao ZichenGao SijingBian YanZhong DengyuanMao Xiaoyun