Ask about this productRelated genes to: PARP12 Blocking Peptide
- Gene:
- PARP12 NIH gene
- Name:
- poly(ADP-ribose) polymerase family member 12
- Previous symbol:
- ZC3HDC1
- Synonyms:
- FLJ22693, PARP-12, ZC3H1
- Chromosome:
- 7q34
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-10
- Date modifiied:
- 2015-11-06
Related products to: PARP12 Blocking Peptide
Related articles to: PARP12 Blocking Peptide
- Methotrexate (MTX)-induced liver injury (MTX-ILI) involves complex mechanisms that remain incompletely understood. This study investigated the role of NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis in MTX-ILI and explored the regulatory involvement of reactive oxygen species (ROS) and mitochondrial permeability transition pore (mPTP) opening. Wistar rats administered MTX and L02 cells exposed to MTX exhibited significant hepatocellular injury and pyroptotic features, as evidenced by elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and Caspase-1 activities; increased interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels; and upregulation of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), gasdermin D (GSDMD), and its N-terminal fragment (GSDMD-N). These effects were attenuated by the NLRP3 inhibitor MCC950. In vitro, scavenging ROS with N-acetylcysteine (NAC) and inhibiting mPTP opening with ciclosporin A (CsA) markedly suppressed pyroptosis by alleviating mitochondrial dysfunction, reducing ROS accumulation, restoring mitochondrial membrane potential, and preserving mitochondrial ultrastructure. Label-free quantitative proteomics and protein-protein interaction analysis identified KNG1 and PARP12 as key proteins associated with ROS/mPTP-mediated pyroptosis, which were validated by Western blotting. Furthermore, Connectivity Map analysis predicted four potential therapeutic agents, including RS-127445, SB-218795, proadifen, and balicatib. Collectively, these findings demonstrate that MTX induces NLRP3-dependent pyroptosis through ROS accumulation and sustained mPTP opening. - Source: PubMed
Publication date: 2026/05/14
Cheng XuechunWu HaoZhuang XiupingYang BaohuiDing MingGao HongdaLi SijieLi QianWang Xin - The immunological composition of the microenvironment has shown relevance for diagnosis, prognosis, and therapy in solid tumors but remains underexplored in acute leukemias. We investigated the significance of the acute myeloid leukemia (AML) bone marrow microenvironment in predicting chemosensitivity and long-term remission in pediatric patients. We analyzed 32 non-promyelocytic pediatric AML patients at diagnosis using a NanoString PanCancer IO 360 assay, RNA sequencing, and deep-phenotype flow cytometry analyses. The findings were validated using the pediatric TARGET AML dataset. A short signature of three interferon (IFN)-related genes (, , and ) distinguished patients with chemosensitive disease and reduced minimal residual disease after induction chemotherapy. The signature stratified patients overall, and within the clinically defined "standard-risk" group, patients with high gene expression at diagnosis had significantly longer overall survival. The leukemia microenvironment associated with this signature showed enrichment of non-exhausted CD4 and CD8 T cytotoxic lymphocytes and expansion of CD8 T effector memory cells re-expressing CD45RA (TEMRA) in patients with a favorable prognosis. Our results show the importance of the bone marrow microenvironment in pediatric AML and provide tools for a refined stratification of "standard-risk" patients, lacking adequate risk-oriented therapies. They also offer a promising guide for tackling immune pathways and exploiting immune-targeted therapies. - Source: PubMed
Publication date: 2026/04/29
Sherif ShimaaAli AeshaIbrahim KhadegaRinchai DarawanElanbari MohammedKizhakayil DhanyaToufiq MohammedVempalli Fazulur RMina TommasoComoli PatriziaGhias KulsoomFadoo ZehraHerrera SheannaLachica Che-AnnDawoud Enas D KBibawi HaniSapia SandraDason BlessingEjaz AnilaAnas Mohammed Y SSaleh AymanGentilcore GiusyBedognetti DavideCugno ChiaraDeola Sara - Poly(ADP-ribose) polymerase (PARP) inhibitors are highly effective therapies for BRCA1/2-mutated tumors. However, most patients eventually develop acquired resistance. Here, we report that JPI-547, a second-generation PARP inhibitor targeting both PARP1/2 and tankyrase, demonstrates potent antitumor activity in olaparib-sensitive and resistant BRCA1/2 mutant models. - Source: PubMed
Publication date: 2026/05/06
Kang Min SilKatuwal Nar BahadurGhosh MithunHong Sa DeokJeong Yeong GyuPark Seong MinKim Tae HoenKim Seul-GiLee Seung RyeolMoon Yong Wha - Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited therapeutic options. Here, we investigated how integrin-dependent signaling pathways regulate tumor metabolism and therapeutic vulnerability in TNBC. Pharmacological inhibition of the integrin/FAK axis and/or BRD4 induced cell cycle arrest, autophagy, and senescence in highly proliferative cells, consistent with a metabolic stress phenotype. Metabolomic analyses using [U-¹³C]-glucose revealed a marked suppression of glycolytic carbon flux, accompanied by an approximately 30-47% reduction in intracellular NAD⁺ levels and coordinated alterations in NADH and tricarboxylic acid (TCA) cycle intermediate α-ketoglutarate. Mechanistically, we identified nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD⁺ biosynthesis, as a central metabolic node integrating signaling/function of the two axes. NAMPT expression/activity was sustained transcriptionally or post-translationally, including sirtuin-associated deacetylation and neddylation-dependent proteasomal turnover. In BRCA1/2-deficient TNBC, integrin-FAK and NAMPT/NAD pathways converged on Wnt/β-catenin signaling to regulate DNA repair, and response to PARP1/2 inhibitors. Co-inhibiting FAK and NAMPT synergistically suppressed tumor growth by approximately 80%. Elevated stromal NAMPT expression was associated with a trend toward favorable clinical outcomes. Collectively, these findings uncover a previously unrecognized crosstalk between integrin/FAK and NAMPT/NAD⁺ pathways in TNBC and identify a synthetic lethal-like therapeutic vulnerability that warrants further evaluation in clinically relevant models. - Source: PubMed
Publication date: 2026/04/29
Spellecy OrionQadir JaveriaHan RongboZhu KaiXu BingweiZhang YangAryal IshaLin Ruei-LungLin An-HsuanFaisal Abu Saleh MosaNapier DanaPiecoro DavaScott TimLin PenghuiChen LiBrewer Lawrence DWang ChiKyprianou NatashaGuo ZhenhengGuo RuihuaThibault OlivierYang Burton BYang Xiuwei H - PARP14 (ARTD8), a unique mono-ADP-ribosyltransferase (mono-ART) in the ADP-ribosyltransferase (ART) superfamily, has emerged as a core regulator of immune signaling and tumor microenvironment (TME), with functions distinct from the canonical DNA repair roles of PARP1/2. This review systematically elucidates the structural basis of PARP14, focusing on its mechanism as a "bimodal transcriptional switch" that enhances signal transducer and activator of transcription (STAT) 6-mediated anti-inflammatory signals while suppressing STAT1-driven interferon responses. We dissect the critical roles of PARP14 in regulating macrophage polarization, lymphocyte fate, and host-virus interactions, revealing how it modulates an immunosuppressive microenvironment and drives metabolic reprogramming. Furthermore, we evaluate the potential of emerging therapeutic strategies, including high-selectivity inhibitors and proteolysis-targeting chimera (PROTAC) degraders, to overcome resistance to immunotherapy. Finally, we highlight that successful clinical translation necessitates resolving tissue-specific paradoxes through targeted delivery and establishing biomarker-based precision stratification systems. - Source: PubMed
Publication date: 2026/04/23
Li SiqiHuang XinyueDeng BoyanWang YanlingWen Ran