Ask about this productRelated genes to: PPM1B antibody
- Gene:
- PPM1B NIH gene
- Name:
- protein phosphatase, Mg2+/Mn2+ dependent 1B
- Previous symbol:
- -
- Synonyms:
- PPC2BETAX, PP2CB, PP2CBETA
- Chromosome:
- 2p21
- Locus Type:
- gene with protein product
- Date approved:
- 1993-02-05
- Date modifiied:
- 2016-10-05
Related products to: PPM1B antibody
Related articles to: PPM1B antibody
- The metal-dependent protein phosphatase (PPM/PP2C) family regulates innate immune and cell death pathways through reversible phosphorylation. Although these enzymes contain a conserved third Mg /Mn ion (M3) that is essential for activity, its chemical role in phosphate hydrolysis has remained unclear. Here, we report studies that reveal PPM1B promotes cell death during infection and utilizes a trinuclear metal center in which M3 directly coordinates the substrate phosphate, positioning it for in-line S 2 hydrolysis. In addition to substrate orientation, M3 positions a water molecule to protonate the departing alkoxide, stabilizing the leaving-group. Functionally, M3 substitutes for the arginine clamp in phosphoprotein phosphatases (PPP), revealing that these evolutionarily distinct phosphatase families have converged on the same chemical strategy through fundamentally different catalytic architectures. Together, these findings define a three-metal mechanism in PPM phosphatases and identify the M3 site as a rare and potentially druggable feature for immune and infectious diseases. - Source: PubMed
Publication date: 2026/04/27
Stevens Reece PSolodushko ViktoriyaWierzbicki AndrzejRich Thomas CAlexeyev Mikael FThompson Marlo KStone MadelineHall CamryndeWeever AltheaSayner Sarah LStevens TroyAndrews JoelPrakash AishwaryaHonkanen Richard ELee Ji YoungSalter E AlanSwingle Mark R - Pulmonary carcinoma remains a highly aggressive malignancy driven by complex signaling and epigenetic dysregulation. This study investigates a novel oncogenic pathway involving the MgMn-dependent protein phosphatase 1B PPM1B/myosin phosphatase (MP)/protein arginine methyltransferase 5 (PRMT5) axis, which promotes carcinogenesis by symmetrically dimethylating histone H2A and suppressing tumor suppressor genes. We hypothesized that loss of PPM1B would activate this pathway and drive tumorigenesis. Western blotting, PCR, and immunohistochemistry revealed a significant reduction in PPM1B expression in both squamous cell carcinoma (SCC) and human lung adenocarcinoma (ADC) compared to normal lung tissues, which correlated with worse patient survival. Despite an increase in total MYPT1, the regulatory subunit of MP, its inhibitory phosphorylation at Thr853 was significantly elevated in both tumor types. The inactivation of MP corresponded with a significant increase in the activating phosphorylation of PRMT5 at Thr80, especially in SCC, which was linked to a particularly poor prognosis. Downstream, this resulted in a dramatic elevation in the symmetric dimethylation of histone H2A, leading to decreased expression of retinoblastoma protein. Our findings demonstrate that decreased PPM1B expression drives the oncogenic activation of the MP/PRMT5 axis. This mechanism contributes to the aggressive nature of SCC, establishing PPM1B as a promising prognostic marker in lung cancer. - Source: PubMed
Publication date: 2025/11/11
Makai AttilaKeller IlkaSzalmás Fanni AUngvári ÁdámHorváth DánielMajor EvelinEnyedi AttilaTakács IstvánLontay Beáta - Papillary thyroid carcinoma (PTC) is usually indolent, but a subset of patients shows aggressive behavior. Understanding protein-level mechanisms is essential for identifying new therapeutic targets. - Source: PubMed
Publication date: 2025/11/04
Wang Shi-QiYang MiaoRao De-WeiSu Yan-JunCheng Ruo-Chuan - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies. PDAC is characterized by prominent necrotic foci within the tumor and a high propensity for distant liver metastasis, leading to a poor prognosis. In this study, using patient-derived organoid models, single-cell RNA sequencing, and multiplex immunofluorescence staining of samples from patients with PDAC, in vivo TGFβ1 conditional knockout mouse models, and 3D in vitro models, we discovered that the formation of intratumoral necrotic foci in pancreatic cancer is closely associated with liver metastatic events. This process was triggered by the deficiency of the long noncoding RNA TRAF3IP2-AS1 that induced necroptosis, which was accompanied by an immunosuppressive microenvironment. Mechanistically, TRAF3IP2-AS1 blocked necroptosis by reducing the mRNA stability of MLKL through competitively binding to IGF2BP2. Loss of TRAF3IP2-AS1 also promoted necroptosis by promoting RIPK3 phosphorylation via interference with the ubiquitination of the phosphatase PPM1B that dephosphorylates RIPK3. Additionally, TRAF3IP2-AS1 deficiency promoted the release of TGFβ1 from tumor cells, which induced an M2-like immunosuppressive phenotype and the release of more TGFβ1. The elevated production of TGFβ1 created a feedback loop that promoted the transcription of TRAF3IP2-AS1 in tumor cells to balance necroptosis. Overall, these findings identify TRAF3IP2-AS1 as a key regulator of necroptosis and the formation of an immunosuppressive microenvironment in PDAC, providing potential therapeutic targets for treating liver metastasis in patients with pancreatic cancer. - Source: PubMed
Wu Yong-DingHuang Xiao-XiaoZhang Hao-XiangPan YuXie Cheng-KeLi GeLin Cai-FengLin Xin-QuanLi Zhi-YuanChen Yin-HaoHu Jian-FeiLin Hong-YiZhu Shun-CangWang Zu-WeiTian Yi-FengLi Qiao-WeiLiao Cheng-YuChen Shi - Cognitive dysfunction poses a significant challenge in clinical practice, but currently available drugs mainly address symptoms and have limited effectiveness in treating cognitive dysfunction associated with various neurological disorders. Mendelian randomization (MR) and colocalization analyses were conducted to explore the causal associations between 4302 druggable genes with blood and brain cis-expression quantitative trait loci (eQTLs) and cognitive performance. The causal effects of candidate druggable genes on brain structure and neurological diseases were assessed to gain insights into the underlying mechanisms. Among over 4000 druggable genes, our study identified causal associations between 72 druggable genes (41 blood eQTLs and 31 brain eQTLs) and cognitive performance. Thirteen eQTLs (six in blood: ERBB3, SPEG, ATP2A1, GDF11, CYP2D6, GANAB; seven in brain: ERBB3, DPYD, TAB1, WNT4, CLCN2, PPM1B, CAMKV) were identified as candidate druggable genes for cognitive performance. Notably, both blood and brain eQTLs of ERBB3 were negatively associated with cognitive performance (blood: OR = 0.933, 95% CI 0.911-0.956, p-value = 9.69E-09; brain: OR = 0.782, 95% CI 0.718-0.852, p-value = 2.13E-08). Moreover, these candidate druggable genes exhibited causal effects on both brain structure and neurological diseases. Our integrative analysis provides genetic evidence supporting candidate therapeutic targets for improving cognitive performance and treating neurological diseases. Furthermore, it sheds light on the possible mechanisms by which these targets affect brain structures. This finding suggested that these identified druggable genes, particularly ERBB3 and CYP2D6, hold promise as potential drug targets for enhancing cognitive performance. - Source: PubMed
Publication date: 2025/06/25
Zhang Lu-YangLiu Yu-XinChu Yun-HuiYou Yun-FanZhou Luo-QiYang ShengDong Ming-HaoZhang HangPang Xiao-WeiChen LianZhu Li-FangXiao JunShang KeWang WeiQin ChuanTian Dai-Shi