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
- Retinal ischemia-reperfusion (I/R), a hallmark feature of many retinal degenerative diseases, often leads to irreversible neuronal damage. Among the various forms of cell death, necroptosis has emerged as a pivotal mechanism contributing to retinal neurodegeneration. Here, we identify a novel regulatory axis that modulates neuronal necroptosis using the long non-coding RNA (lncRNA) Pvt1. Using both (R28 cell line) and (intravitreal injection of adeno-associated virus carrying lncRNA Pvt1 shRNA in rats) models, the role of lncRNA Pvt1 under I/R and oxygen-glucose deprivation/reperfusion (OGD/R) is assessed. Comprehensive molecular and cellular analyses show that I/R or OGD/R induce robust necroptotic responses in neuronal cells. Notably, lncRNA Pvt1 knockdown significantly alleviates these necroptotic phenotypes by inhibiting RIPK3 phosphorylation. Mechanistically, lncRNA Pvt1 knockdown reduces promoter methylation, restoring PPM1B expression. Subsequently, PPM1B protein upregulation facilitates RIPK3 dephosphorylation, effectively dampening the necroptosis signaling cascade. These findings reveal that the previously unrecognized lncRNA Pvt1/PPM1B/p-RIPK3 axis is essential for neuronal survival following ischemic stress. This study provides compelling evidence that targeting the lncRNA Pvt1 is a promising therapeutic strategy for mitigating retinal neuronal necroptosis. Modulating this pathway provides new opportunities for the treatment of I/R-related retinal diseases. - Source: PubMed
Publication date: 2026/08/17
Xia XiaojingChen QiyuCheng ZeyuHu WenqiTan YunQing NanLiu JiaqiHuang KaiHu BoShang Lei - The spatiotemporal regulation of protein phosphorylation regulates cellular homeostasis, yet the phosphatase networks that actively dismantle oncogenic kinase signaling remain elusive. Here, we identify Mg-dependent protein phosphatase 1 (PPM1B) as a critical tumor suppressor in cervical carcinoma. Biochemically, PPM1B directly interacts with and dephosphorylates the myosin phosphatase (MP) regulatory subunit MYPT1 at its inhibitory Thr853 residue. We show that Rho-associated kinase (ROCK) activation by lysophosphatidic acid generates a high-affinity substrate profile, recruiting PPM1B to the Thr853-phosphorylated MYPT1. Crucially, this dephosphorylation drives the nuclear export of the MP holoenzyme, triggering a dual tumor-suppressive cascade. In the cytoplasm, reactivated MP dephosphorylates myosin light chain (MLC20) at Ser19 to prevent actomyosin-driven invasion. Concurrently, nuclear clearance of MYPT1 disrupts the PRMT5/histone H4 epigenetic axis, diminishing PRMT5 Thr80 phosphorylation and H4 symmetric dimethylation. Proteomic and phospho-kinase profiling indicates that PPM1B globally reprograms the malignant state, upregulating tumor suppressors (p53, Maspin) while attenuating epithelial-mesenchymal transition (EMT) drivers and survival networks (JNK, CREB). Finally, clinical biopsies of human squamous cell carcinoma demonstrate a strong correlation between reduced PPM1B expression and MYPT1 Thr853 hyperphosphorylation. Collectively, our findings establish PPM1B as a master catalytic switch that abrogates oncogenic signaling at both the cytoskeletal and epigenetic levels. - Source: PubMed
Publication date: 2026/08/08
Ungvári ÁdámKeller IlkaKinter RichárdKónya ZoltánNagyenyedi Zoltán ÖdönDemény MátéErdődi FerencKiss AndreaLontay Beata - 5-Fluorouracil (5-FU) is a first-line chemotherapy commonly used to treat colorectal cancer (CRC). However, the development of acquired resistance to 5-FU remains a significant clinical challenge, and the underlying epigenetic mechanisms are not fully understood. In this study, we demonstrate that euchromatic histone lysine methyltransferase 2 (EHMT2) is significantly upregulated in CRC patients with poor responses to 5-FU, directly correlating with lower overall survival rates. Using established 5-FU resistant (5-FUR) HCT116 and HT29 cell lines, RNA-sequencing confirmed robust EHMT2 overexpression compared with wild-type cells. Mechanistically, siRNA-mediated knockdown of EHMT2 restored 5-FU sensitivity by upregulating protein phosphatase 1B (PPM1B), a key downstream target. This EHMT2-PPM1B axis disruption effectively induced G1 phase cell cycle arrest and triggered apoptosis in 5-FUR cells, fundamentally impairing their proliferation. Furthermore, we validated the therapeutic potential of targeting this pathway using in vivo and ex vivo models. Combination treatment with 5-FU and the specific pharmacological EHMT2 inhibitor (BIX-01294) synergistically suppressed tumor growth in a 5-FUR cell-derived xenograft mouse model. Importantly, these therapeutic effects were faithfully recapitulated in 5-FUR patient-derived colorectal cancer organoid (PDO) models. Together, our findings elucidate a critical epigenetic mechanism where EHMT2 promotes 5-FU drug resistance. Targeting EHMT2 represents a promising and translatable therapeutic strategy for overcoming chemoresistance and improving clinical outcomes in CRC patients. - Source: PubMed
Publication date: 2026/05/18
Tae In HwanKang YunsangLee JinkwonLee Jeong MinKim JinsanLee Su-GiPark KunhyangRyu Tae YoungKim KwanghoKim GyeonghwaSon TaesangLee Hye WonKim SolbiLee Hyo JinJung Cho-RokLim Jung HwaLee Moo-SeungHur KeunHan Tae-SuKim Dae-SooSon Mi-YoungCho Hyun-Soo - 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 S2 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