{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTK4 (also known as MST1) acts as a master regulator of cellular stress responses by initiating diverse pro‐apoptotic and anti‐autophagic signaling cascades. Upon activation by a range of stressors, STK4 phosphorylates key substrates such as Beclin1—thereby inhibiting autophagy in cardiomyocytes (e.g., via Thr108 modification)—as well as histone H2AX, FOXO transcription factors, and regulators of the p53 pathway. These phosphorylation events trigger chromatin condensation, mitochondrial‐dependent apoptosis, and β‑cell dysfunction in diabetes. Moreover, STK4 activity is fine‐tuned by upstream kinases like Akt that phosphorylate inhibitory sites to restrain its action, and by phosphatase regulated events that further modulate its capacity to trigger cascades leading to caspase activation and enhanced oxidative stress. This intricate network of post‐translational modifications underlies STK4’s critical role in dictating cell fate in the heart, neurons, and other tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in stress‐induced cell death, STK4 is indispensable for the maintenance and function of the immune system. It governs T‑ and B‑cell survival and homeostasis such that loss‐of‐function mutations lead to combined immunodeficiency syndromes marked by lymphopenia, augmented apoptotic responses in lymphocytes, and impaired naïve T‑cell maintenance via deregulation of FOXO1 and IL‑7 receptor expression. STK4 also modulates innate immune signaling by curbing antiviral responses through phosphorylation of key mediators like IRF3, while in macrophages it limits proinflammatory cytokine secretion—actions that collectively help prevent chronic inflammation and its downstream pathologies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in regulating cell death and immune homeostasis, STK4 functions as a pivotal tumor suppressor and developmental regulator. Aberrant expression or epigenetic silencing of STK4 has been implicated in a range of malignancies—including hematologic cancers, pancreatic, cervical, colorectal, and gliomas—where its loss promotes unchecked cell proliferation, impairs apoptosis, alters mitotic fidelity (via deregulation of kinetochore–microtubule attachments), and disrupts mitochondrial homeostasis and mitophagy. In developmental contexts, STK4 contributes to proper ciliogenesis and endothelial tip cell polarity during sprouting angiogenesis, while in settings such as renal ischemia–reperfusion injury and endometriosis, its regulation of mitochondrial fission and cytoskeletal dynamics determines cell survival under stress. Furthermore, STK4 can be targeted by oncoproteins or regulatory miRNAs (for example, via miR‑18a in HPV‑associated cervical cancer), underscoring its multifaceted roles in both normal physiology and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "45"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yenshou Lin, Andrei Khokhlatchev, Daniel Figeys, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M202630200"}], "href": "https://doi.org/10.1074/jbc.M202630200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12384512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12384512"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "P M de Souza, M A Lindsay "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian Sterile20-like kinase 1 and the regulation of apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST0320485"}], "href": "https://doi.org/10.1042/BST0320485"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15157167"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15157167"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sung-Wuk Jang, Seung-Ju Yang, Shanthi Srinivasan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M704542200"}], "href": "https://doi.org/10.1074/jbc.M704542200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17726016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17726016"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bekir Cinar, Ping-Ke Fang, Mohini Lutchman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601872"}], "href": "https://doi.org/10.1038/sj.emboj.7601872"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17932490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17932490"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anton Vichalkovski, Ekaterina Gresko, Hauke Cornils, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NDR kinase is activated by RASSF1A/MST1 in response to Fas receptor stimulation and promotes apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2008.10.060"}], "href": "https://doi.org/10.1016/j.cub.2008.10.060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19062280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19062280"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zengqiang Yuan, Maria K Lehtinen, Paola Merlo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of neuronal cell death by MST1-FOXO1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M900461200"}], "href": "https://doi.org/10.1074/jbc.M900461200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19221179"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19221179"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Juhyun Choi, Sangphil Oh, Dongjun Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mst1-FoxO signaling protects Naïve T lymphocytes from cellular oxidative stress in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0008011"}], "href": "https://doi.org/10.1371/journal.pone.0008011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19956688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19956688"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Meng Qiao, Yaqi Wang, Xiaoen Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.03.017"}], "href": "https://doi.org/10.1016/j.molcel.2010.03.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20513427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20513427"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Weihong Wen, Feng Zhu, Jishuai Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MST1 promotes apoptosis through phosphorylation of histone H2AX."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.151753"}], "href": "https://doi.org/10.1074/jbc.M110.151753"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20921231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20921231"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Cai Guo, Xiaoying Zhang, Gerd P Pfeifer "}, {"type": "b", "children": [{"type": "t", "text": "The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.178210"}], "href": "https://doi.org/10.1074/jbc.M110.178210"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21199877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21199877"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Fang Yuan, Qi Xie, Junbing Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.182543"}], "href": "https://doi.org/10.1074/jbc.M110.182543"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21212262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21212262"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ingrid Babel, Rodrigo Barderas, Ramón Diaz-Uriarte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of MST1/STK4 and SULF1 proteins as autoantibody targets for the diagnosis of colorectal cancer by using phage microarrays."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M110.001784"}], "href": "https://doi.org/10.1074/mcp.M110.001784"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21228115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21228115"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "A Morinaka, Y Funato, K Uesugi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oligomeric peroxiredoxin-I is an essential intermediate for p53 to activate MST1 kinase and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.139"}], "href": "https://doi.org/10.1038/onc.2011.139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21516123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21516123"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yeping Zhou, Youri Adolfs, W W M Pim Pijnappel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MICAL-1 is a negative regulator of MST-NDR kinase signaling and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01389-10"}], "href": "https://doi.org/10.1128/MCB.01389-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21730291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21730291"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Filiz Kisaayak Collak, Kader Yagiz, Daniel J Luthringer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Threonine-120 phosphorylation regulated by phosphoinositide-3-kinase/Akt and mammalian target of rapamycin pathway signaling limits the antitumor activity of mammalian sterile 20-like kinase 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.358713"}], "href": "https://doi.org/10.1074/jbc.M112.358713"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22619175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22619175"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Sonali Jalan Rawat, Caretha L Creasy, Jeffrey R Peterson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tumor suppressor Mst1 promotes changes in the cellular redox state by phosphorylation and inactivation of peroxiredoxin-1 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.414524"}], "href": "https://doi.org/10.1074/jbc.M112.414524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23386615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23386615"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Yasuhiro Maejima, Shiori Kyoi, Peiyong Zhai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3322"}], "href": "https://doi.org/10.1038/nm.3322"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24141421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24141421"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Amin Ardestani, Federico Paroni, Zahra Azizi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3482"}], "href": "https://doi.org/10.1038/nm.3482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24633305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24633305"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Hongyan Li, Jianxun Feng, Yunfang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mst1 deletion attenuates renal ischaemia-reperfusion injury: The role of microtubule cytoskeleton dynamics, mitochondrial fission and the GSK3β-p53 signalling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2018.10.012"}], "href": "https://doi.org/10.1016/j.redox.2018.10.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30384260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30384260"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Erinna F Lee, Nicholas A Smith, Tatiana P Soares da Costa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into BCL2 pro-survival protein interactions with the key autophagy regulator BECN1 following phosphorylation by STK4/MST1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2018.1564557"}], "href": "https://doi.org/10.1080/15548627.2018.1564557"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30626284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30626284"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Nadine T Nehme, Jana Pachlopnik Schmid, Franck Debeurme, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-09-378364"}], "href": "https://doi.org/10.1182/blood-2011-09-378364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22174160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22174160"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Hengameh Abdollahpour, Giridharan Appaswamy, Daniel Kotlarz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The phenotype of human STK4 deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-09-378158"}], "href": "https://doi.org/10.1182/blood-2011-09-378158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22294732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22294732"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Sevil Oskay Halacli, Deniz Cagdas Ayvaz, Cagman Sun-Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STK4 (MST1) deficiency in two siblings with autoimmune cytopenias: A novel mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clim.2015.06.010"}], "href": "https://doi.org/10.1016/j.clim.2015.06.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26117625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26117625"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Jiang Li, Xingrong Du, Hao Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mammalian Sterile 20-like Kinase 1 (Mst1) Enhances the Stability of Forkhead Box P3 (Foxp3) and the Function of Regulatory T Cells by Modulating Foxp3 Acetylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.668442"}], "href": "https://doi.org/10.1074/jbc.M115.668442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26538561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26538561"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Weiyun Li, Jun Xiao, Xin Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STK4 regulates TLR pathways and protects against chronic inflammation-related hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI81203"}], "href": "https://doi.org/10.1172/JCI81203"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26457732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26457732"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Fansen Meng, Ruyuan Zhou, Shiying Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.277533.116"}], "href": "https://doi.org/10.1101/gad.277533.116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27125670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27125670"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Alexander Hergovich, Reto S Kohler, Debora Schmitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2009.09.020"}], "href": "https://doi.org/10.1016/j.cub.2009.09.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19836237"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19836237"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Hyun Jung Oh, Mi Ju Kim, Su Jung Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MST1 limits the kinase activity of aurora B to promote stable kinetochore-microtubule attachment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2009.12.054"}], "href": "https://doi.org/10.1016/j.cub.2009.12.054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20171103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20171103"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Amber L Couzens, James D R Knight, Michelle J Kean, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions."}]}, {"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.2004712"}], "href": "https://doi.org/10.1126/scisignal.2004712"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24255178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24255178"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Francesca Cottini, Teru Hideshima, Chunxiao Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3562"}], "href": "https://doi.org/10.1038/nm.3562"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24813251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24813251"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Zhiqiang Lin, William T Pu "}, {"type": "b", "children": [{"type": "t", "text": "Harnessing Hippo in the heart: Hippo/Yap signaling and applications to heart regeneration and rejuvenation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.scr.2014.04.010"}], "href": "https://doi.org/10.1016/j.scr.2014.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24881775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24881775"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Kun Liang, Guangxi Zhou, Qi Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of hippo pathway in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Saudi J Gastroenterol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4103/1319-3767.133025"}], "href": "https://doi.org/10.4103/1319-3767.133025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24976283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24976283"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Miju Kim, Minchul Kim, Mi-Sun Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms6370"}], "href": "https://doi.org/10.1038/ncomms6370"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25367221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25367221"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Yuewen Chao, Yan Wang, Xuejiao Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurooncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11060-014-1654-4"}], "href": "https://doi.org/10.1007/s11060-014-1654-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25373346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25373346"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "L Li, R Fang, B Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deacetylation of tumor-suppressor MST1 in Hippo pathway induces its degradation through HBXIP-elevated HDAC6 in promotion of breast cancer growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.476"}], "href": "https://doi.org/10.1038/onc.2015.476"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26657153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26657153"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Amin Ardestani, Kathrin Maedler "}, {"type": "b", "children": [{"type": "t", "text": "MST1: a promising therapeutic target to restore functional beta cell mass in diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-016-3892-9"}], "href": "https://doi.org/10.1007/s00125-016-3892-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27053234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27053234"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Amber L Couzens, Shawn Xiong, James D R Knight, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MOB1 Mediated Phospho-recognition in the Core Mammalian Hippo Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M116.065490"}], "href": "https://doi.org/10.1074/mcp.M116.065490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28373298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28373298"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Qi Li, Feng Qi, Xiangchao Meng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mst1 regulates colorectal cancer stress response via inhibiting Bnip3-related mitophagy by activation of JNK/p53 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Toxicol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10565-017-9417-6"}], "href": "https://doi.org/10.1007/s10565-017-9417-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29063978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29063978"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Jiekai Yu, Xiaohui Zhai, Xiaofen Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of MST1 as a potential early detection biomarker for colorectal cancer through a proteomic approach."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-14539-x"}], "href": "https://doi.org/10.1038/s41598-017-14539-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29079854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29079854"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Qingdong Zhao, Mingxia Ye, Wen Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000487450"}], "href": "https://doi.org/10.1159/000487450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29448246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29448246"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Yoo Hyung Kim, Jeongwoon Choi, Myung Jin Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A MST1-FOXO1 cascade establishes endothelial tip cell polarity and facilitates sprouting angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-08773-2"}], "href": "https://doi.org/10.1038/s41467-019-08773-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30783090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30783090"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Jiujie Cui, Zhuqing Zhou, Haiyan Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-18-0910"}], "href": "https://doi.org/10.1158/1541-7786.MCR-18-0910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30796177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30796177"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Ethan L Morgan, Molly R Patterson, Emma L Ryder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1008624"}], "href": "https://doi.org/10.1371/journal.ppat.1008624"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32555725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32555725"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Yang Tang, Gemin Fang, Fenghua Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2020.05.019"}], "href": "https://doi.org/10.1016/j.ccell.2020.05.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32589942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32589942"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "S Pauliina Turunen, Pernilla von Nandelstadh, Tiina Öhman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2-dependent apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-019-0321-x"}], "href": "https://doi.org/10.1038/s41418-019-0321-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30903103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30903103"}]}]}]}