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
- 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 - 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