Ask about this productRelated genes to: PPM1A antibody
- Gene:
- PPM1A NIH gene
- Name:
- protein phosphatase, Mg2+/Mn2+ dependent 1A
- Previous symbol:
- -
- Synonyms:
- MGC9201, PP2Calpha, PP2CA
- Chromosome:
- 14q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1993-02-05
- Date modifiied:
- 2015-11-20
Related products to: PPM1A antibody
Related articles to: PPM1A antibody
- Carbohydrate moieties profoundly influence target binding, drug-like properties, and mechanism of action, but achieving site-selective editing within complex oligosaccharide chains remains a challenge for conventional chemical methods. We herein report an enzymatic deglycosylation platform that enables precise, site-selective removal of sugar units from branched carbohydrate chains of dammarane-type saponins, the first reported PPM1A phosphatase agonists. SAR analysis confirms the distal xylose removal drastically improves PPM1A agonistic potency versus the parent saponins. Cellular and in vivo assays prove the optimized derivative represses PPM1A-governed TGF-β1/Smad3 and NF-κB p65 phosphorylation. In diverse hepatic fibrosis models, it alleviates fibrotic progression dose-dependently, matching the efficacy of the clinical drug resmetirom at equivalent doses and administration regimens. In conclusion, our findings establish a versatile toolbox for precise modifications of complex carbohydrate moieties under mild conditions and delineate the critical role of specific glycosyl groups in modulating PPM1A activity as a therapeutic strategy for hepatic fibrosis. - Source: PubMed
Publication date: 2026/07/10
Wang HanghangLi QiWang WenxiuJin ZechengTong XinyiZhang YuLiu YueHan HuifaYang MengWu DaleiHu LihongZhuang JingjingZhao LinguoZhang Yinan - Protein phosphatase PPM1A plays a critical role in cellular signaling by dephosphorylating key regulatory proteins. According to experimental data, the enzyme requires either Mn or Mg bound in the active center(s), hence its catalytic activity strongly depends on the chelated metal ions. In this study, the metal ion selectivity of PPM1A is investigated using DFT calculations on active site constructs of bi- and trinuclear metal centers and protein ligands from the first and second metal coordination shells. Binuclear Mn-Mn and trinuclear Mn-Mn-Mn sites show poor resistance to substitution by biogenic Fe and Zn, with Gibbs energies of the Mn → Fe/Zn exchange being consistently negative in both the gas phase and condensed media. In contrast, Mg-Mg and Mg-Mg-Mg centers are substantially more robust, with a thermodynamically unfavorable Mg → Fe/Zn substitution-except in the case of the Mg-Mg-Zn complex. The primary factors governing this metal competition in the modeled structures are the nature of the competing cation and the solvation properties of its aqua complexes, while solvent exposure of the binding site and the number of metal cations in the catalytic center exert a comparatively minor effect. Overall, these findings demonstrate that Mg-loaded active sites offer considerably greater protection against biogenic metal displacement than their Mn counterparts, thus shedding light on the metalloprotein stability and enzyme fidelity of PPM1A. - Source: PubMed
Publication date: 2026/06/11
Kircheva NikoletaPetkova VladislavaAngelova SilviaDudev Todor - Local goose breeds Shitou and Wuzong exhibit distinct growth rates, implying divergent embryonic muscle development. This study used embryonic myoblasts from the Magang goose, an established model with superior growth traits, to explore the underlying common regulatory mechanisms. Extending our previous findings that 5-AZA (DNA methylation inhibitor) and BC339 (DNA hydroxylation inhibitor) oppositely affect myoblast proliferation and differentiation, we performed whole-transcriptome sequencing on inhibitor-treated goose embryonic myoblasts. This aimed to identify DNA methylation-mediated ncRNA-mRNA networks governing myoblast fate, with key interactions being functionally validated. - Source: PubMed
Publication date: 2026/06/18
Luo YongquanHong PufeiChen TiandeLi YongHan YuanhaoChang KaiyueLiu ZiyangLi XiujinHuang YunmaoTian YunboWu ZhongpingZhang Xumeng - Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a severe side effect lacking effective treatment, largely due to its complex and poorly understood pathogenesis. Here, we observed the pathological inhibition of phosphatase PPM1A activity in the dorsal root ganglia (DRG) tissues of PIPN mice. We also found that otilonium bromide (OB), as a PPM1A activator, ameliorated the PIPN-like pathology in mice, as evidenced by the alleviation of sensory dysfunction, myelin sheath injury, intraepidermal nerve fiber loss and vascular lesions. Using PPM1A-specific knockdown mice, we demonstrated that OB suppresses pro-inflammatory M1 macrophage polarization in the DRG through the PPM1A/NF-κB/NLRP3/IL-1β pathway, thereby alleviating axonal degeneration and neuronal apoptosis. In vitro experiments revealed that PTX-damaged DRG neurons release high-mobility group box 1 (HMGB1) to promote pro-inflammatory macrophage polarization, while OB disrupts this neuron-macrophage interaction by limiting HMGB1 release and subsequent macrophage activation. Together, our findings highlight PPM1A activation as a promising therapeutic strategy for PIPN and identify OB as a potential agent for treating this clinical side effect. - Source: PubMed
Publication date: 2026/05/07
Liu XiaojingZhang MengZhang YueHao YiningLu DayunLi WenjunShen Xu - Natural products are biologically active compounds used for therapeutic interventions for various diseases, particularly infections. Autophagy is an intracellular catabolic pathway involving lysosomal degradation and is closely associated with immunological pathways, effectively combating bacterial, viral, fungal, and parasitic infections. Accumulating evidence suggests that autophagy activation or inhibition by natural products promotes antimicrobial responses against various pathogens. Numerous natural products can modulate autophagy through diverse signaling pathways, suggesting their potential as a host-directed therapeutic strategy that may complement conventional drug regimens or help mitigate drug resistance in various infectious diseases. However, it remains largely unclear whether these effects are mediated by direct modulation of autophagy or indirectly through associated mechanisms, including enhanced immune defense, attenuation of pathological inflammation, or crosstalk with other organelle functions. Additionally, multiple pathogens can evade host responses; thus, autophagy activation may inadvertently create favorable conditions for certain pathogens. This review discusses the current knowledge of natural products in terms of their antimicrobial actions through autophagy regulation, particularly the roles of distinct natural product classes, such as polyphenols, alkaloids, terpenoids, quinones, peptides, and macrolides in modulating autophagy for potentially contributing to control various infectious diseases. Exploring the intricate molecular interplay between natural products and autophagy in limiting infections may provide valuable insights that could inform the development of innovative host-directed antimicrobial treatments based on autophagy regulation. 3-MA: 3-methyladenine; AM: alveolar macrophages; AMP: antimicrobial peptides; AMPK: 5' adenosine monophosphate-activated protein kinase; ARDS: acute respiratory distress syndrome; ART: artemisinin; ASFV: African swine fever virus; ATG: autophagy related; AZM: azithromycin; BafA1: bafilomycin A; BECN1: beclin 1; BMDM: bone marrow-derived macrophage; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2; CBD: cannabidiol; CF: cystic fibrosis; CGA: chlorogenic acid; CGAS: cyclic GMP-AMP synthase; CHUK/IKKα: component of inhibitor of nuclear factor kappa B kinase complex; CLP: cecal ligation and puncture; CLR: clarithromycin; CMA: chaperone-mediated autophagy; CoV: coronavirus; DHT: dihydrotanshinone I; EGCG: epigallocatechin-3-gallate; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK2: eukaryotic translation initiation factor 2 alpha kinase 2; ESKAPE: , and spp.; ESRRA: estrogen related receptor alpha; FOXO1: forkhead box O1; FUNDC1: FUN14 domain containing 1; HBV: hepatitis B virus; HCV: hepatitis C virus; HDT: host-directed therapy; HIV: human immunodeficiency virus; HMGB1: high mobility group box 1; HSV: herpes simplex virus; IAV: influenza A virus; ICT: isocryptotanshinone; IFN: interferon; IKBKB/IKKβ: inhibitor of nuclear factor kappa B kinase subunit beta; IL: interleukin; INH: isoniazid; IRF3: IFN regulatory factor 3; KEAP1: kelch like ECH associated protein 1; LAMP: lysosomal associated membrane protein; LAP: LC3-associated phagocytosis; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MDM: monocyte-derived macrophage; MDR: multidrug-resistant; MON: monotropein; Mtb: ; MTOR: mechanistic target of rapamycin kinase; mtROS: mitochondrial ROS; NET: neutrophil extracellular trap; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; NFKB/NF-κB: nuclear factor kappa B; NLRP3: NLR family pyrin domain containing 3; NLRX1: NLR family member X1; NOTCH1: notch receptor 1; NTM: nontuberculous mycobacteria; OMS: ohmyungsamycin; PAK1: p21 (RAC1) activated kinase 1; PINK1: PTEN induced kinase 1; PKM/PKM2: pyruvate kinase M1/2; PLD: phospholipase D; PM: peritoneal macrophage; PPM1A: protein phosphatase, Mg2+/Mn2+ dependent 1A; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PTEN: phosphatase and tensin homolog; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RELA/p65: RELA proto-oncogene, NF-kB subunit; RIF: rifampicin; ROS: reactive oxygen species; RSV: resveratrol; RUBCN/rubicon: rubicon autophagy regulator; SAR: selective autophagy receptor; SIRT: sirtuin; STING1: stimulator of interferon response cGAMP interactor 1; STX17: syntaxin 17; Tat: trans-activator of transcription; TB: tuberculosis; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TLR: toll like receptor; TNA: tanshinone IIA; TNF: tumor necrosis factor; UA: ursolic acid; ULK1/Atg1: unc-51 like autophagy activating kinase 1; UPR: unfolded protein response; UVRAG: UV radiation resistance associated; VAMP8: vesicle associated membrane protein 8; VDR: vitamin D receptor; WIPI2: WD repeat domain, phosphoinositide interacting 2; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1; ZIKV: Zika virus. - Source: PubMed
Publication date: 2026/04/28
Paik SeungwhaUm SoohyunKim In SooPark Eun-JinKim Kyung TaeBasu JoyotiOh Dong-ChanJo Eun-Kyeong