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Last update 08 May 2025

PPM1B

Last update 08 May 2025

Basic Info

Synonyms

PP2C-beta, PP2CB, PP2CBETA

+ [5]

Introduction

Enzyme with a broad specificity. Dephosphorylates CDK2 and CDK6 in vitro. Dephosphorylates PRKAA1 and PRKAA2. Inhibits TBK1-mediated antiviral signaling by dephosphorylating it at 'Ser-172'. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.

Drugs associated with PPM1B

HN252

Target

PPM1B

Mechanism

PPM1B inhibitors

Active Org.-

Originator Org.

Shandong University

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PPM1B

100 Translational Medicine associated with PPM1B

0 Patents (Medical) associated with PPM1B

103

Literatures (Medical) associated with PPM1B

01 Feb 2025·Journal of Biological Chemistry

Magnesium-dependent-protein phosphatase 1B regulates the protein arginine methyltransferase 5 through the modulation of myosin phosphatase

Article

Author: Horváth, Dániel ; Kónya, Zoltán ; Kiss, Andrea ; Tóth, Emese ; Ungvári, Ádám ; Keller, Ilka ; Erdődi, Ferenc ; Major, Evelin ; Lontay, Beáta

Dysregulation of the expression levels and the activity of kinases/phosphatases is an intrinsic hallmark of tumor transformation and progression, as either as a primary cause or consequence. The myosin phosphatase (MP)/protein arginine methyltransferase 5 (PRMT5)/histone (H4) pathway is an oncogenic signaling pathway downregulating the gene expression of tumor suppressors. However, the upstream regulators of the pathway are unknown. We show that the Mg²⁺-dependent protein phosphatase 1 B (PP2Cb or PPM1B) interacts and regulates MP through the MYPT1 regulatory subunit, and this interplay results in the inactivation of the tumorigenic pathway driven by PRMT5. The phospho-Thr696 inhibitory residues of the MYPT1 regulatory subunit of MP was dephosphorylated by PPM1B. The inhibition of PPM1B by sanguinarine resulted in the deactivation of MP and the increased activity of PRMT5 leading to increased symmetric dimethylation of histone H4 in HeLa cells. The overexpression of the PPM1B had the opposite action. The overexpression of PPM1B decreased the colonization activity of HeLa cells through modulation of MP. Finally, human cervical carcinoma biopsies showed almost complete elimination of PPM1B compared to their healthy control counterparts. The phosphorylation of the inhibitory MYPT1^pT696 and the regulatory PRMT5^pT80 residues and the symmetric dimethylation of H4 were elevated in the cancer biopsies and it resulted in a decrease in retinoblastoma protein expression. The results indicate a tumor suppressor role of the PPM1B/MP axis via inhibition of PRMT5, thereby regulating gene expression through H4 arginine dimethylation. Collectively, PPM1B is a tumor suppressor and a possible tumor marker for cervical carcinoma.

31 Jan 2025·Circulation Research

BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-β Pathway Activation Promote High-Fat/High-Sucrose Diet–Induced Arterial Stiffness

Article

Author: Zuo, Min ; Bai, Yongping ; Li, Mengke ; Wang, Hu ; Liu, Yanan ; Zhao, Ziyan ; Bao, Kaiwen ; Yan, Meng ; Chen, Zhipeng ; Ai, Ding ; Jiang, Hongfeng

BACKGROUND: Metabolic syndrome heightens cardiovascular disease risk primarily through increased arterial stiffness. We previously demonstrated the involvement of YAP (Yes-associated protein) in high-fat/high-sucrose diet (HFHSD)–induced arterial stiffness via modulation of PPM1B (protein phosphatase Mg 2+ /Mn 2+ –dependent 1B)-lysine 63(K63) deubiquitination. In this study, we aimed to elucidate the role and mechanisms underlying PPM1B deubiquitination in HFHSD-induced arterial stiffness. METHODS:Enzymes governing PPM1B deubiquitination were identified through small interfering RNA (siRNA) screening and mass spectrometry. Glutathione S-transferase pull-down, coimmunoprecipitation, protein purification, and immunofluorescence were used to explore the mechanism underlying PPM1B deubiquitination. Doppler ultrasound was used to evaluate HFHSD-induced arterial stiffness in mice, and telemetry was used to record pulsatile (systolic and diastolic) blood pressure.RESULTS: Smooth muscle cell–specific PPM1B overexpression attenuated HFHSD-induced arterial stiffness in mice in a PPM1B-K326-K63–linked polyubiquitination-dependent manner. Mechanistically, ABRO1 (Abraxas brother 1; a core BRCC36 [BRCA1/BRCA2 (breast cancer type 1/2)–containing complex subunit 36] isopeptidase complex component) directly bound YAP and underwent liquid-liquid phase separation with YAP and PPM1B in a YAP-dependent manner, which in turn promoted PPM1B deubiquitination. Furthermore, smooth muscle cell–specific Abro1 -knockout mice and Brcc3 -knockout mice showed attenuated HFHSD-induced arterial stiffness and activation of transforming growth factor-β–Smad (mothers against decapentaplegic homolog) signaling. CONCLUSIONS:We elucidated the PPM1B deubiquitination mechanisms and highlighted a potential therapeutic target for metabolic syndrome–related arterial stiffness.

01 Nov 2024·Heliyon

RNAs m6A modification facilitates UVB-induced photoaging

Article

Author: Tan, Lina ; Yan, Siyu ; Wu, Meng ; Lu, Tingting ; Zhang, Shuping ; Tian, Xiaoying ; Gao, Lihua ; Zeng, Jinrong ; Wang, Dan

RNA N6-methylation (m⁶A) modification is common in eukaryotic mRNA and has been linked to various physiological disorders, including UVB-induced photoaging. To identify biological differences among photoaging. Three pairs of normal and photoaged skin tissues were collected for m⁶A RNA sequencing assay. Transcriptome profiles showed differential m⁶A methylation modifications in 1365 mRNAs in photoaging skin tissues. Pathway analysis revealed the involvement of cellular stress response and regulation of cell cycle G2/M phase transition in m⁶A-mRNAs. Further experiments validated the differential expression of m⁶A methyltransferases (METTL3 and METTL14) and hypermethylation modification in mRNAs (CENPE, PPM1B and TPM1). In vitro studies demonstrated that increased METTL3 and METTL14 levels promoted m⁶A methylation of CENPE, PPM1B and TPM1 in UVB-induced photoaging cells, and further experiments on mice showed that downregulation of METTL3 and METTL14 reduced m⁶A modifications in CENPE, PPM1B and TPM1, leading to the delayed appearance of photoaging phenotypes, suggesting that these genes could serve as potential therapeutic targets for treating photoaging. Our study characterized key transcriptome changes in photoaging and identified the role of METTL3 and METTL14 in mediating m⁶A modification, resulting in the upregulation of CENPE, PPM1B and TPM1 expression, which may be crucial in UVB-induced photoaging.

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PPM1B

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