Ask about this productRelated genes to: UPF1 antibody
- Gene:
- UPF1 NIH gene
- Name:
- UPF1 RNA helicase and ATPase
- Previous symbol:
- RENT1
- Synonyms:
- HUPF1, KIAA0221, NORF1, pNORF1, smg-2
- Chromosome:
- 19p13.11
- Locus Type:
- gene with protein product
- Date approved:
- 1997-02-11
- Date modifiied:
- 2019-01-25
Related products to: UPF1 antibody
Related articles to: UPF1 antibody
- Resistance to anti-PD-1 immunotherapy remains a critical challenge in colorectal cancer (CRC). However, the functional role of S100A14 in CRC remains controversial regarding its oncogenic status and impact on immunotherapy response. Here, integrating single-cell RNA sequencing and tissue microarray analysis, we definitively identify S100A14 as an oncogenic driver of immunotherapy resistance. High S100A14 expression correlates with poor prognosis and an immunosuppressive "cold" tumor phenotype. Mechanistically, S100A14 directly binds UPF1, a core nonsense-mediated mRNA decay (NMD) factor, promoting its ubiquitination-mediated degradation. This impairs the decay of non-canonical NF-κB transcripts (MAP3K14, NFKB2, RELB), causing constitutive pathway activation and PD-L1 upregulation. In co-culture assays, S100A14-overexpressing cells directly suppressed CD8 T-cell cytotoxicity by downregulating GZMB and induced exhaustion via PD-1 upregulation. In syngeneic mouse models, S100A14 overexpression accelerated hepatic metastasis and conferred anti-PD-1 resistance by suppressing GZMB CD8 T-cell infiltration and promoting Treg recruitment. Notably, restoring UPF1 expression reversed malignant phenotypes in vitro and rescued S100A14-mediated immune evasion in co-culture models. Collectively, we define the S100A14-UPF1-non-canonical NF-κB axis as a actionable mechanism driving immune evasion in CRC. - Source: PubMed
Publication date: 2026/06/25
Tan LiDai XinglongWu YujuanZuo ZhongCheng Yong - RNA helicases are central architects of ribonucleoprotein (RNP) organization, coupling nucleoside triphosphate hydrolysis to RNA binding to unwind duplexes, translocate along nucleic acids, displace RNA-binding proteins, and remodel RNP assemblies. Among them, UPF1 (UP-Frameshift 1) is a highly conserved superfamily 1 (SF1) helicase and the pivotal effector of nonsense-mediated mRNA decay (NMD). UPF1 harbors the canonical helicase core motifs required for ATP binding and hydrolysis, RNA interaction, and chemo-mechanical coupling, as well as regulatory domains that fine-tune its catalytic activity and protein-protein interactions. UPF1 displays remarkable enzymatic versatility, acting as an RNA translocase, helicase and RNPase. Its capacity to coordinate these distinct but interconnected activities enables dynamic remodeling of messenger RNPs and positions UPF1 as a multifunctional regulator of RNA fate during NMD. In this review, we integrate current structural and mechanistic insights into UPF1 function and propose a unifying framework that links its biochemical properties to its diverse cellular roles, aiming to reconcile the existing models that describe its mechanism of action. - Source: PubMed
Publication date: 2026/06/24
Mocquet VincentFiorini Francesca - Exosomes serve as critical mediators in driving therapeutic resistance among tumor cells by delivering bioactive molecules, including circular RNAs (circRNAs). Through bioinformatics mining of public databases, we identified circ_0097112 as a circular RNA implicated in icotinib resistance in lung adenocarcinoma (LUAD). Our subsequent experiments revealed that circ_0097112 was specifically upregulated in EGFR-TKI-resistant cells and in their secreted exosomes. To elucidate the functional role of circ_0097112 in EGFR-TKI-resistant lung cancer cells, we conducted in vitro experiments demonstrating that circ_0097112 promotes proliferation and concomitantly suppresses apoptosis in LUAD cells. Confocal microscopy revealed that drug-resistant lung cancer cells encapsulate circ_0097112 within exosomal vesicles and horizontally transfer this cargo to drug-sensitive recipient cells, thereby conferring acquired resistance. To delineate the mechanistic basis by which circ_0097112 confers drug resistance, we integrated bioinformatic prediction with experimental validation, including RNA pull-down and RNA immunoprecipitation assays. Our findings demonstrated that circ_0097112 directly interacts with UPF1 protein to assemble a functional complex, thereby suppressing decay of oncogenic NRAS. This molecular event consequently activates downstream RAF/MAPK signaling, attenuating apoptosis while promoting cellular proliferation and drug resistance. Collectively, this study reveals the pivotal involvement of the circ_0097112/UPF1/NRAS axis in driving EGFR-TKI resistance in LUAD and offers a new theoretical basis for targeting circ_0097112 to reverse EGFR-TKI resistance. - Source: PubMed
Publication date: 2026/06/06
Chen ZiyuanWang YuXu YierWang ShuaibinXu ZhiyuanTang XingpingKang BailamuZhou ChengweiMeng Xiaodan - - Source: PubMed
Publication date: 2026/05/15
Wang YixiaoSun HuiHou XiaoyaXing WenluXu ZhengguoZhang QingsongYang Bo - Ferroptosis induction is a novel strategy for treating human cancers; however, the detailed mechanisms underlying ferroptosis resistance during nasopharyngeal carcinoma (NPC) progression remain unclear. Herein, we explored the role and potential mechanism of LINC00839 in ferroptosis resistance of NPC cells. We found that the expression levels of LINC00839 and transcription factor ets-like kinase 1 (ELK1) were elevated in NPC tissues, which were associated with a poor survival of NPC patients. Overexpression of LINC00839 or ELK1 reduced the sensitivity of NPC cells to ferroptosis-inducing drugs. Mechanistically, ELK1 directly bound to LINC00839 promoter to contribute to its transcription. Subsequently, LINC00839 destabilized ring finger and CHY zinc finger domain-containing 1 (RCHY1) mRNA through recruitment of up-frameshift 1 (UPF1), and consequently inhibited ubiquitination and degradation of DJ-1 protein. LINC00839 knockdown induced NPC cell ferroptosis, which was neutralized by RCHY1 depletion or DJ-1 overexpression. Knockdown of ELK1 or LINC00839 exerted synergistic roles with Erastin or ferroptosis-inducing chemotherapeutic drug Sorafenib to enhance ferroptosis, thereby delaying tumor growth in vivo. In summary, this study reveals that ELK1-mediated transcription activation of LINC00839 promotes ferroptosis resistance of NPC cells by destabilizing RCHY1 mRNA and subsequent repressing DJ-1 ubiquitination and degradation. These findings provide potential therapeutic targets for overcoming ferroptosis resistance in NPC. - Source: PubMed
Publication date: 2026/05/14
Liu FengLi YuLiu HuaiTang LingFang ShuWenWang XiChen PanWang HuiBao MeiHuaHe BinShengGuo Zhen