{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPM1A functions as a key negative regulator of transforming growth factor‐β (TGF‐β) and bone morphogenetic protein (BMP) signaling pathways by selectively dephosphorylating receptor‐activated Smads. In doing so, it terminates TGF‐β–induced Smad2/3 and BMP–induced Smad1 signaling, facilitates nuclear export, and thereby dampens transcriptional responses that underlie normal developmental processes as well as pathological events. Moreover, through its interaction with nuclear envelope proteins such as MAN1 and its modulation by posttranslational events like myristoylation (regulated by CSIG), PPM1A establishes a feedback loop that tightly controls Smad activation and the amplitude as well as duration of signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the Smad pathways, PPM1A also attenuates pro‐inflammatory and innate immune signals by dephosphorylating key components of the nuclear factor‐κB (NF‐κB) cascade—such as IKKβ and the RelA subunit—as well as by targeting STING and TBK1 to balance antiviral responses. In addition, it regulates transcriptional elongation via removal of phosphate from the T-loop of Cdk9, thereby modulating P-TEFb function and influencing processes like HIV-1 proviral transcription."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn immune cells, PPM1A exerts multifaceted roles by modulating the differentiation and survival of monocytes/macrophages. Its elevated expression in infected macrophages—whether in the context of Mycobacterium tuberculosis infection alone or during HIV-1/Mtb co-infection—suppresses apoptotic signals (notably via JNK inactivation) and blunts antibacterial responses. Additionally, extracellular PPM1A can function as a damage-associated molecular pattern that, through TLR4–MyD88 signaling, stimulates pro-inflammatory cytokine release in conditions such as rheumatoid arthritis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn oncogenesis and fibrotic conditions, PPM1A generally serves as a tumor suppressor and antifibrotic factor. Its loss—often through ubiquitin-mediated degradation induced by viral proteins (such as HBx), specific microRNAs, or E3 ubiquitin ligases (e.g., TRIM59)—leads to sustained TGF-β signaling, enhanced cell invasion and metastasis, and poorer clinical outcomes in cancers including hepatocellular carcinoma, pancreatic ductal adenocarcinoma, oral squamous cell carcinoma, and gastric cancer. Reduced expression of PPM1A is also associated with fibrotic responses in the kidney, where its diminished activity permits SMAD3-mediated induction of fibrosis. Similar deregulations have been noted in other pathological settings such as gestational trophoblastic disease, where altered PPM1A levels are predictive of malignant transformation, and in viral contexts like HCV-associated oncogenesis, where its tumor suppressor features are emerging."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and mechanistic studies have provided crucial insights into PPM1A’s catalytic activity. Crystallographic and biophysical analyses reveal that the enzyme requires binding of three metal ions—with coordinating residues such as Asp146, Asp239, Arg33, and Arg186 playing critical roles in substrate recognition and active site conformation. Such structural determinants, as well as regulatory posttranslational modifications (including phosphorylation, ubiquitination by proteins like TRIM59, and regulation by long noncoding RNAs such as TSPEAR-AS2), modulate PPM1A’s stability and specificity. In addition, PPM1A targets metabolic regulators by dephosphorylating PPARγ at Ser273, thereby influencing diabetic gene expression and metabolic homeostasis, while extracellular roles have been implicated in pathological bone formation in ankylosing spondylitis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xia Lin, Xueyan Duan, Yao-Yun Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2006.03.044"}], "href": "https://doi.org/10.1016/j.cell.2006.03.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16751101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16751101"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xueyan Duan, Yao-Yun Liang, Xin-Hua Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein serine/threonine phosphatase PPM1A dephosphorylates Smad1 in the bone morphogenetic protein signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M605169200"}], "href": "https://doi.org/10.1074/jbc.M605169200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16931515"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16931515"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shizhong Bu, Bagrat Kapanadze, Tien Hsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Opposite effects of dihydrosphingosine 1-phosphate and sphingosine 1-phosphate on transforming growth factor-beta/Smad signaling are mediated through the PTEN/PPM1A-dependent pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802417200"}], "href": "https://doi.org/10.1074/jbc.M802417200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18482992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18482992"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Benjamin Bourgeois, Bernard Gilquin, Carine Tellier-Lebègue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of TGF-β signaling at the nuclear envelope: characterization of interactions between MAN1, Smad2 and Smad3, and PPM1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.2003411"}], "href": "https://doi.org/10.1126/scisignal.2003411"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23779087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23779087"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jiang Geng, Jie Fan, Qi Ouyang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of PPM1A expression enhances invasion and the epithelial-to-mesenchymal transition in bladder cancer by activating the TGF-β/Smad signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.2144"}], "href": "https://doi.org/10.18632/oncotarget.2144"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25026293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25026293"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Junjie Wang, Lisa Tucker-Kellogg, Inn Chuan Ng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The self-limiting dynamics of TGF-β signaling in silico and in vitro, with negative feedback through PPM1A upregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Comput Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pcbi.1003573"}], "href": "https://doi.org/10.1371/journal.pcbi.1003573"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24901250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24901250"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Feng Zhu, Nan Xie, Zhe Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Cellular Senescence-Inhibited Gene Is Essential for PPM1A Myristoylation To Modulate Transforming Growth Factor β Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00414-18"}], "href": "https://doi.org/10.1128/MCB.00414-18"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30201805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30201805"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wenjing Sun, Yang Yu, Gianpietro Dotti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2008.09.012"}], "href": "https://doi.org/10.1016/j.cellsig.2008.09.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18930133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18930133"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "X Lu, H An, R Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPM1A is a RelA phosphatase with tumor suppressor-like activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2013.246"}], "href": "https://doi.org/10.1038/onc.2013.246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23812431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23812431"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zexing Li, Ge Liu, Liwei Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPM1A regulates antiviral signaling by antagonizing TBK1-mediated STING phosphorylation and aggregation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1004783"}], "href": "https://doi.org/10.1371/journal.ppat.1004783"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25815785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25815785"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yan Wang, Eugene C Dow, Yao-Yun Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M807495200"}], "href": "https://doi.org/10.1074/jbc.M807495200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18829461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18829461"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sona Budhiraja, Rajesh Ramakrishnan, Andrew P Rice "}, {"type": "b", "children": [{"type": "t", "text": "Phosphatase PPM1A negatively regulates P-TEFb function in resting CD4(+) T cells and inhibits HIV-1 gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Retrovirology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1742-4690-9-52"}], "href": "https://doi.org/10.1186/1742-4690-9-52"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22727189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22727189"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Kaitlyn Schaaf, Samuel R Smith, Alexandra Duverger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mycobacterium tuberculosis exploits the PPM1A signaling pathway to block host macrophage apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep42101"}], "href": "https://doi.org/10.1038/srep42101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28176854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28176854"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jim Sun, Kaitlyn Schaaf, Alexandra Duverger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase, Mg2+/Mn2+-dependent 1A controls the innate antiviral and antibacterial response of macrophages during HIV-1 and Mycobacterium tuberculosis infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.8190"}], "href": "https://doi.org/10.18632/oncotarget.8190"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27004401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27004401"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Samuel R Smith, Kaitlyn Schaaf, Nusrah Rajabalee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The phosphatase PPM1A controls monocyte-to-macrophage differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-18832-7"}], "href": "https://doi.org/10.1038/s41598-017-18832-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29343725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29343725"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Beomgu Lee, You Seon Song, Christopher Rhodes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase magnesium-dependent 1A induces inflammation in rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.11.112"}], "href": "https://doi.org/10.1016/j.bbrc.2019.11.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31791585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31791585"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Yuan Liu, Yong Xu, Hongxin Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.8884"}], "href": "https://doi.org/10.18632/oncotarget.8884"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27121309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27121309"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Fengyu Wang, Haili Wang, Lei Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM59 inhibits PPM1A through ubiquitination and activates TGF-β/Smad signaling to promote the invasion of ectopic endometrial stromal cells in endometriosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00127.2019"}], "href": "https://doi.org/10.1152/ajpcell.00127.2019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32348176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32348176"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Chang Liu, Weiping Sun, Kui Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of TRIM65 suppressed the proliferation and invasiveness of gastric cancer cells by restricting the ubiquitin degradation of PPM1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2022.113154"}], "href": "https://doi.org/10.1016/j.yexcr.2022.113154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35421368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35421368"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Lishan Wang, Shuqing Ge, Futing Zhou "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-487a-3p inhibits the growth and invasiveness of oral squamous cell carcinoma by targeting PPM1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1884396"}], "href": "https://doi.org/10.1080/21655979.2021.1884396"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33724144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33724144"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Jie Fan, Michelle X Yang, Qi Ouyang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphatase PPM1A is a novel prognostic marker in pancreatic ductal adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humpath.2016.05.002"}], "href": "https://doi.org/10.1016/j.humpath.2016.05.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27195906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27195906"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Rohan Samarakoon, Alexandra Rehfuss, Nidah S Khakoo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201500105R"}], "href": "https://doi.org/10.1096/fj.201500105R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27328942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27328942"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Jiaqi Tang, Roel Goldschmeding, Rohan Samarakoon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase Mg"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " /Mn"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " dependent-1A and PTEN deregulation in renal fibrosis: Novel mechanisms and co-dependency of expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.201902015RR"}], "href": "https://doi.org/10.1096/fj.201902015RR"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31909517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31909517"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Baohua Zhang, Zhi Zhou, Haiyan Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase 1A (PPM1A) is involved in human cytotrophoblast cell invasion and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-009-0601-5"}], "href": "https://doi.org/10.1007/s00418-009-0601-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19404668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19404668"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Sha-sha Zhang, Xiao-yun Wan, Cai-yun Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Expression and significance of LMP2 and PPM1A in gestational trophoblastic disease]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Fu Chan Ke Za Zhi (2011)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22041443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22041443"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Patrick C Flannery, Kodye L Abbott, Satyanarayana R Pondugula "}, {"type": "b", "children": [{"type": "t", "text": "Correlation of PPM1A Downregulation with CYP3A4 Repression in the Tumor Liver Tissue of Hepatocellular Carcinoma Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Drug Metab Pharmacokinet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13318-019-00595-3"}], "href": "https://doi.org/10.1007/s13318-019-00595-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31792727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31792727"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Yali Zhou, Yan Zhao, Yaoying Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatitis C virus NS3 protein enhances hepatocellular carcinoma cell invasion by promoting PPM1A ubiquitination and degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-017-0510-8"}], "href": "https://doi.org/10.1186/s13046-017-0510-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28283039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28283039"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Kan Tanoue, Lisa M Miller Jenkins, Stewart R Durell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Binding of a third metal ion by the human phosphatases PP2Cα and Wip1 is required for phosphatase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi4005649"}], "href": "https://doi.org/10.1021/bi4005649"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23906386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23906386"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Subrata Debnath, Dalibor Kosek, Harichandra D Tagad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A trapped human PPM1A-phosphopeptide complex reveals structural features critical for regulation of PPM protein phosphatase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA117.001213"}], "href": "https://doi.org/10.1074/jbc.RA117.001213"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29602904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29602904"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Sharlyn J Mazur, Elyssia S Gallagher, Subrata Debnath, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Conformational Changes in Active and Inactive States of Human PP2Cα Characterized by Hydrogen/Deuterium Exchange-Mass Spectrometry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.biochem.6b01220"}], "href": "https://doi.org/10.1021/acs.biochem.6b01220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28481111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28481111"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Itsumi Tani, Shogo Ito, Yukiko Shirahata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of active site arginine residues in substrate recognition by PPM1A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.10.001"}], "href": "https://doi.org/10.1016/j.bbrc.2021.10.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34637963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34637963"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Keon Woo Khim, Sun Sil Choi, Hyun-Jun Jang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPARγ at Ser273."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells9020343"}], "href": "https://doi.org/10.3390/cells9020343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32024237"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32024237"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Mao Li, Xingfeng Xu, Yan Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A comprehensive overview of PPM1A: From structure to disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Biol Med (Maywood) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/15353702211061883"}], "href": "https://doi.org/10.1177/15353702211061883"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34861123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34861123"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Subin Weon, Sungsin Jo, Bora Nam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular PPM1A promotes mineralization of osteoblasts differentiation in ankylosing spondylitis via the FOXO1A-RUNX2 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.17685"}], "href": "https://doi.org/10.1111/jcmm.17685"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36756789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36756789"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Yi-Chao Xia, Jun Cao, Jing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Markers (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/2217663"}], "href": "https://doi.org/10.1155/2021/2217663"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34336002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34336002"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Peng Cheng, Yongbin Wang, Qian Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of TRIM59 in regulating PPM1A in the pathogenesis of silicosis and the intervention effect of tanshinone IIA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2024.117014"}], "href": "https://doi.org/10.1016/j.biopha.2024.117014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38908195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38908195"}]}]}]}