Ask about this productRelated genes to: PI16 antibody
- Gene:
- PI16 NIH gene
- Name:
- peptidase inhibitor 16
- Previous symbol:
- -
- Synonyms:
- MGC45378, dJ90K10.5, MSMBBP, CD364
- Chromosome:
- 6p21.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-29
- Date modifiied:
- 2016-10-05
Related products to: PI16 antibody
Related articles to: PI16 antibody
- Host factors that promote or restrict human immunodeficiency virus (HIV) infection in human CD4+ T cells have not been comprehensively identified. We employed orthogonal genome-wide CRISPR activation (CRISPRa) and CRISPR knockout screens in primary CD4+ T cells to discover pro- and anti-HIV host factors systematically. Secondary pooled screens and individual perturbations validated high-confidence hits and revealed diverse mechanisms of action. CRISPRa uncovered multiple potent antiviral factors, including PI16, PPID, SHISA3, and ITM2A. PI16 interacts with host factors involved in HIV fusion and inhibits viral entry, whereas PPID (Cyp40), a paralog of the proviral cyclophilin CypA, binds capsid and reduces nuclear import of the HIV core. Structural modeling, evolutionary analyses, and targeted mutagenesis revealed domains and residues required for PPID-mediated HIV restriction, including non-human primate ortholog substitutions that enhance antiviral activity. Together, these data define the functional HIV-host interaction landscape in primary human T cells and uncover new mechanisms modulating infection. - Source: PubMed
Publication date: 2026/04/20
Rathore UjjwalDugan EliThornton HunterKumar Vigneshwari EaswarDajani RamaBurdick Ryan CYoung Janet MSteinhart ZacharyLao ReannaDelviks-Frankenberry Krista AChoi WooyoungHenriques William SEcheverria IgnaciaDann EmmaDureja IshaanPathak NandiniArce Maya MMcKetney JustinUmhoefer Jennifer MParulekar SimrunSchmidt RalfPolacco Benjamin JNeidleman JasonMontano MauricioNguyen Vinh QSali AndrejLevy Jay ATenthorey Jeannette LCheng YifanRoan Nadia RSwaney Danielle LKaake Robyn MDodgson Stacie EHiatt JosephPathak Vinay KMalik Harmit SKrogan Nevan JMarson Alexander - Atherosclerosis, a major cause of adverse cardiovascular events and mortality rates worldwide, stems from sustained lipid accumulation and subsequent chronic inflammation within the arterial walls. An early identification of patients at risk is crucial to prevent life-threatening thrombotic events and provide effective and personalized treatments. Leveraging the power of machine learning (ML) to enhance diagnostics and biomarker discovery, we applied a high-throughput approach using five ML classification algorithms (MLCA), integrating clinical and serum proteomic data from patients with carotid atherosclerotic stenosis (AT, n:60), dyslipidemic patients (DLP, n:55), and healthy controls (HC, n:66). As a result, a robust 6-protein panel (B2M, GPV, MMP9, PLF4, TSP1, and FB isoforms) was identified with a ROC-AUC value > 0.9 for all algorithms applied, highly discriminating AT patients compared to DLP or CTRL. The levels of these proteins were further validated in an independent external cohort, including patients presenting with acute atherothrombotic stroke, corroborating the potential of this panel as biomarker for atherosclerosis severity. In addition, the combined clinical-proteomic ML approach provided a more accurate patient stratification than the clinical or proteomic analysis alone. Mechanistically, the identified biomarkers highlight the importance of platelet activation, uncontrolled angiogenesis and intraplaque haemorrhage in the atherosclerotic process, underscoring the need for multipathway therapies to prevent unwanted thrombotic events. - Source: PubMed
Publication date: 2026/04/10
Extremera-García Mª JesúsRojas-Torres MartaPriego-Torres BlancaBeltrán-Camacho LucíaEslava-Alcón SaraRodríguez-Martín FranciscoBenítez-Camacho JosefaBallesteros-Ribelles AntonioDel Val Ana MartínezOlsen JesperLozano-Loaiza EvaGonzález-García Mª ÁngelaSanchez-Morillo DanielFernández-Vega AlejandroMontaner JoanDoiz EstherRodriguez-Piñero ManuelDurán-Ruiz Mª Carmen - DICER1-related tumor predisposition (DRTP), also known as DICER1 syndrome, encompasses a spectrum of malignancies mainly in children and young adults. Most are sarcomas, exhibiting histological and molecular similarities regardless of their anatomical origins, and only express the RNase IIIb domain-defective DICER1. To uncover their cellular origin and developmental hierarchy, we establish a lineage-traceable genetically engineered mouse model with controlled activation of hemizygous Dicer1 RNase IIIb mutation in Hic1 mesenchymal stromal cells. This causes renal tumors closely mirroring the developmental continuum of human DRTP sarcoma histologically and molecularly. Spatial single-cell transcriptomic analysis reveals a Hic1PdgfraDptPi16 fibroblastic progenitor population, corresponding to universal fibroblasts subjacent to transitional epithelium of renal collecting ducts, that can undergo rhabdomyoblastic differentiation or become proliferative sarcomatous cells. Investigation of patient samples identifies analogous cell states and developmental trajectories. This study uncovers a fibroblastic origin for DRTP sarcoma and provides a faithful mouse model for future mechanistic and translational investigation. - Source: PubMed
Publication date: 2026/03/30
Kommoss Felix K FZhang Joyce Yu HanLynch Branden JChen Shary YutingSenz JanineMoscovitz YanaHill Lesley AMa DingScott R WilderBush JonathanChen Kenneth SRoth Andrewvon Deimling AndreasFoulkes William DMorin Gregg BUnderhill T MichaelWang YeminHuntsman David G - Non-small cell lung cancer (NSCLC) exhibits disparate responses to anti-angiogenic therapies between its two major histologic subtypes, lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), suggesting a histotype-dependent angiogenesis regulation. Tumor-associated fibroblasts (TAFs) exhibit an activated/myofibroblast-like phenotype in NSCLC, and are emerging as major regulators of tumor progression; yet, their role in controlling angiogenesis in NSCLC remains undefined. Here we analyzed angiogenesis/hypoxia markers in NSCLC, and combined transcriptomics (bulk RNA-seq, scRNA-seq), angiogenesis arrays, genetic perturbations and functional in vitro and in vivo assays to dissect the histotype-dependent production of pro-angiogenic factors in TAFs. We observed greater angiogenesis and reduced necrosis/hypoxia in LUAD compared to LUSC across multiple patient cohorts. The LUAD-TAF secretome was primed for angiogenesis through SMAD3-dependent overproduction of key regulators, particularly TIMP-1 and VEGF-A. We also uncovered a novel function for TIMP-1 in promoting endothelial cell hyperbranching over basal VEGF signaling. Conversely, LUSC-TAFs displayed diminished angiogenic effects despite upregulating HIF-1α and a hypoxia-associated transcriptional signature, owing to their lower SMAD3 and compensatory increase in SMAD2. Our study unveils the critical influence of TAFs in shaping the distinct angiogenic landscapes in LUAD and LUSC through the opposing SMAD2/3 regulation of TIMP-1, VEGF-A and hypoxia signaling. These results also highlight the therapeutic potential of targeting stromal SMAD3/TIMP-1 in LUAD or microenvironmental stressors such as hypoxia and acidosis in LUSC. In addition, these findings provide a biological framework for understanding the histotype-dependent patterns of dissemination, immune evasion, and response to anti-angiogenic therapies in NSCLC. - Source: PubMed
Publication date: 2026/03/30
Díaz-Valdivia NataliaDuch PaulaIkemori RafaelParker Amelia LArshakyan MarselinaLlorente AlejandroBernardo AlejandroRodríguez-Rojas JoséCarrasco Josep LluisPark DanielleSahai ErikFillat CristinaJuan ManelNadal ErnestReguart NoemíRadisky Derek CCasanovas OriolAlcaraz Jordi - Melanoma accounts for over 85% of all skin cancer deaths. Current therapies including drugs targeting BRAF and MEK significantly improve the prognosis of metastatic melanoma patients, yet innate or acquired resistance challenges long-term responses. We have shown previously that fatty acid beta-oxidation (FAO) is up-regulated during the acquisition of BRAF-inhibitor (BRAFi) resistance and that the FDA approved drug ranolazine, by targeting FAO attenuates the development of acquired resistance. However, how ranolazine-induced metabolic rewiring increases cell death is unclear. Here we identify ranolazine as a ferroptosis inducer in BRAFi-resistant melanoma, in which FAO serves as a ferroptosis surveillance mechanism. Accordingly, in progressed tumours of BRAFi treated patients up-regulation of FAO regulators correlates with increased expression of ferroptosis markers. BRAFi resistant cells are heavily poised for execution of ferroptosis; they display reduced glutathione levels, higher levels of long-chain polyunsaturated fatty acid (PUFA) membrane-incorporation, and increased membrane-resident phospholipid oxidation, all of which is amplified by ranolazine. Counteracting ranolazine action is MBOAT1/2 mediated phospholipid remodelling, which initiates reduced PUFA membrane-incorporation as ferroptosis surveillance mechanism. We show that the androgen receptor (AR), which is a determinant of BRAFi resistance, controls MBOAT1/2 expression, thereby contributing to ferroptosis resistance. In BRAFi resistant tumours and cell lines, we confirm AR upregulation predominantly in the MITF/AXL undifferentiated/neural-crest like state, but it also occurs in the MITF/AXL differentiated melanocytic state. The AR antagonist enzalutamide sensitises AR expressing melanoma cells to RSL3 and erastin independent of phenotype state, but in FAO BRAFi relapsed tumours AR up-regulation correlates with the undifferentiated/neural-crest like (UD/NC) state, and enzalutamide synergises with ranolazine in ferroptosis-induction in UD/NC cells. Thus, therapeutically combining ranolazine with the AR inhibitor enzalutamide to induce ferroptosis can circumvent dedifferentiation related BRAFi resistance and could increase therapeutic activity and long-term efficacy. - Source: PubMed
Publication date: 2026/03/23
Redondo-Muñoz MartaCaballe-Mestres AdriaReisz Julie AValero-Leria AneOlias-Arjona AnaAldaz PaulaD Alessandro AngeloWellbrock ClaudiaArozarena Imanol