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Apoptosis AND MST1

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https://www.readbyqxmd.com/read/28552397/morin-attenuates-diethylnitrosamine-induced-rat-liver-fibrosis-and-hepatic-stellate-cell-activation-by-co-ordinated-regulation-of-hippo-yap-and-tgf-%C3%AE-1-smad-signaling
#1
Perumal NaveenKumar, Perumal MadanKumar, Halagowder Devaraj, Sivasithamparam NiranjaliDevaraj
Despite great progress in understanding the activation of hepatic stellate cells (HSCs) during liver fibrosis, therapeutic approaches to inhibit HSC activation remain very limited. Recent reports highlight Yes-associated protein (Yap) and transforming growth factor-β1 (TGF-β1) as critical regulators of HSC activation and henceforth a compound targeting Hippo/Yap and TGF-β1/Smad pathways would be a potential anti-fibrotic candidate. Morin, a dietary flavonoid, was earlier reported to inhibit HSC proliferation and induction of apoptosis of cultured HSCs, mainly by suppressing Wnt/β-catenin and NF-κB signaling, but its effect on Hippo/Yap and TGF-β1/Smad pathways was not determined...
May 25, 2017: Biochimie
https://www.readbyqxmd.com/read/28534197/pcmt1-ameliorates-neuronal-apoptosis-by-inhibiting-the-activation-of-mst1-after-subarachnoid-hemorrhage-in-rats
#2
Ligen Shi, Ammar Al-Baadani, Keren Zhou, Anwen Shao, Shenbin Xu, Sheng Chen, Jianmin Zhang
Mammalian sterile 20-like kinase 1 (MST1) is found to promote neuronal apoptosis. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1), an anti-apoptosis factor, was recently identified as an MST1-interacting protein. This study aims to explore the potential role of PCMT1 in reducing MST1-induced neuronal apoptosis after subarachnoid hemorrhage (SAH) in rats. One hundred ninety-eight male Sprague-Dawley rats were used. An exogenous PCMT1 agonist, CGP 3466B, was injected subcutaneously 1 h after the SAH induced by endovascular perforation...
May 22, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28487119/the-mammalian-ste20-like-kinase-1-mst1-is-a-substrate-for-the-apoptosis-inhibiting-protein-kinase-ck2
#3
Christina Servas, Sandra Kiehlmeier, Julia Hach, Rebecca Gross, Claudia Götz, Mathias Montenarh
Apoptosis and the response to cell stress are evolutionary highly conserved mechanisms. Both processes require strict regulation, which is often performed by protein kinases. The mammalian Sterile 20-like kinase 1 (MST1) is a pro-apoptotic protein kinase, which is activated and cleaved by caspases upon the induction of cell stress. Being a phosphoprotein itself, the activity of MST1 is regulated by phosphorylation. Protein kinase CK2 is an anti-apoptotic protein kinase which seems to be involved in the regulation of many different cellular processes including apoptosis...
May 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28480597/melatonin-protects-against-diabetic-cardiomyopathy-through-mst1-sirt3-signaling
#4
Mingming Zhang, Jie Lin, Shanjie Wang, Zheng Cheng, Jianqiang Hu, Tingting Wang, Wanrong Man, Tao Yin, Wenyi Guo, Erhe Gao, Russel J Reiter, Haichang Wang, Dongdong Sun
The present study investigated the effects of melatonin on diabetic cardiomyopathy (DCM) and determined the underlying mechanisms. Echocardiography indicated that melatonin notably mitigated the adverse left ventricle remodeling and alleviated cardiac dysfunction in DCM. The mechanisms were attributed to increased autophagy, reduced apoptosis and alleviated mitochondrial dysfunction. Furthermore, melatonin inhibited Mst1 phosphorylation and promoted Sirt3 expression in DCM. These results indicated that melatonin may exert its effects through Mst1/ Sirt3 signaling...
May 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28469576/plant-produced-asialo-erythropoietin-restores-pancreatic-beta-cell-function-by-suppressing-mammalian-sterile-20-like-kinase-mst1-and-caspase-3-activation
#5
Elena Arthur, Farooqahmed S Kittur, Yuan Lin, Chiu-Yueh Hung, David C Sane, Jiahua Xie
Pancreatic beta-cell death adversely contributes to the progression of both type I and II diabetes by undermining beta-cell mass and subsequently diminishing endogenous insulin production. Therapeutics to impede or even reverse the apoptosis and dysfunction of beta-cells are urgently needed. Asialo-rhuEPO, an enzymatically desialylated form of recombinant human erythropoietin (rhuEPO), has been shown to have cardioprotective and neuroprotective functions but with no adverse effects like that of sialylated rhuEPO...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28454447/inhibitory-effect-and-mechanism-of-exogenous-mammalian-sterile-20-like-kinase-1-on-the-growth-of-human-colorectal-cancer
#6
Jian Wu, Xiaohong Yang, Hongfei Lu, Liqiao Liu, Baohua Xu, Shuangyan Zheng, Bo Yu, Kemin Jie, Fusheng Wan
The present study aimed to observe the inhibitory effect and preliminary mechanism of exogenous mammalian sterile 20-like kinase 1 (MST1) on the growth of colorectal cancer SW480 cells. The SW480 cells were randomly divided into the following groups: Control, empty enhanced green fluorescent protein (EGFP) plasmid (pEGFP-N1), MST1 EGFP plasmid (pEGFP-MST1), 20 µmol/l fluorouracil (5-FU) and pEGFP-MST1 + 5-FU. An MTS colorimetric assay was used to detect cell viability, Hoechst 33342 staining was used to observe cell apoptosis, and western blotting and immunohistochemistry were used to detect the levels of the proteins MST1, yes-associated protein (YAP), phospho-YAP1 (Ser127), p53 and p53 upregulated modulator of apoptosis (PUMA)...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28448802/ddk-promotes-tumor-chemoresistance-and-survival-via-multiple-pathways
#7
Nanda Kumar Sasi, Arjun Bhutkar, Nathan J Lanning, Jeffrey P MacKeigan, Michael Weinreich
DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA replication at individual origins and is composed of CDC7 kinase and its regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor cell lines and primary tumors, and this is correlated with poor prognosis. Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a largely unknown mechanism. Firstly, to understand why DDK is often overexpressed in tumors, we identified gene expression signatures that correlate with DDK high- and DDK low-expressing lung adenocarcinomas...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28366538/morin-impedes-yap-nuclear-translocation-and-fosters-apoptosis-through-suppression-of-wnt-%C3%AE-catenin-and-nf-%C3%AE%C2%BAb-signaling-in-mst1-overexpressed-hepg2-cells
#8
NaveenKumar Perumal, MadanKumar Perumal, Anbarasu Kannan, Kumar Subramani, Devaraj Halagowder, NiranjaliDevaraj Sivasithamparam
Recent clinical and experimental evidences strongly acclaim Yes-associated protein (Yap), a key oncogenic driver in liver carcinogenesis, as a therapeutic target. Of the known multiple schemes to inhibit Yap activity, activation of Mammalian Sterile 20-like Kinase 1 (Mst1), an upstream regulator of Yap, appears to be a promising one. In this study, we hypothesize that morin, a bioflavonoid, mediates its anti-cancer effect through the activation of Mst1/hippo signaling in liver cancer cells. To test this hypothesis, both full length Mst1 (F-Mst1) and kinase active N-terminal Mst1 (N-Mst1)-overexpressed HepG2 cells were used...
March 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28210902/deletion-of-mammalian-sterile-20-like-kinase-1-attenuates-neuronal-loss-and-improves-locomotor-function-in-a-mouse-model-of-spinal-cord-trauma
#9
Pan-Feng Wang, Da-Yuan Xu, Yuntong Zhang, Xiao-Bin Liu, Yan Xia, Pan-Yu Zhou, Qing-Ge Fu, Shuo-Gui Xu
Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28150487/structural-insights-into-the-regulation-of-hippo-signaling
#10
Leah Cairns, Thao Tran, Jennifer M Kavran
During development, the Hippo pathway regulates the balance between cell proliferation and apoptosis to control organ size. Appropriate Hippo signaling is associated with stem cell maintenance, while inappropriate signaling can result in tumorigenesis and cancer. Cellular and genetic investigations have identified core components and determined that complex formation and protein phosphorylation are crucial regulatory events. The recent spate of high-resolution structures of Hippo pathway components have begun to reveal the molecular mechanisms controlling these events, including the molecular determinates of complex formation between YAP and TEAD, the role of phosphorylation in controlling complex formation by Mob, and the conformational changes accompanying Mst1/2 kinase domain activation...
March 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28003097/hippo-signaling-in-the-liver-regulates-organ-size-cell-fate-and%C3%A2-carcinogenesis
#11
REVIEW
Sachin H Patel, Fernando D Camargo, Dean Yimlamai
The Hippo signaling pathway, also known as the Salvador-Warts-Hippo pathway, is a regulator of organ size. The pathway takes its name from the Drosophila protein kinase, Hippo (STK4/MST1 and STK3/MST2 in mammals), which, when inactivated, leads to considerable tissue overgrowth. In mammals, MST1 and MST2 negatively regulate the transcriptional co-activators yes-associated protein 1 and WW domain containing transcription regulator 1 (WWTR1/TAZ), which together regulate expression of genes that control proliferation, survival, and differentiation...
February 2017: Gastroenterology
https://www.readbyqxmd.com/read/27716844/sarah-domain-mediated-mst2-rassf-dimeric-interactions
#12
Goar Sánchez-Sanz, Bartłomiej Tywoniuk, David Matallanas, David Romano, Lan K Nguyen, Boris N Kholodenko, Edina Rosta, Walter Kolch, Nicolae-Viorel Buchete
RASSF enzymes act as key apoptosis activators and tumor suppressors, being downregulated in many human cancers, although their exact regulatory roles remain unknown. A key downstream event in the RASSF pathway is the regulation of MST kinases, which are main effectors of RASSF-induced apoptosis. The regulation of MST1/2 includes both homo- and heterodimerization, mediated by helical SARAH domains, though the underlying molecular interaction mechanism is unclear. Here, we study the interactions between RASSF1A, RASSF5, and MST2 SARAH domains by using both atomistic molecular simulation techniques and experiments...
October 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27696525/melatonin-alleviates-postinfarction-cardiac-remodeling-and-dysfunction-by-inhibiting-mst1
#13
Jianqiang Hu, Lei Zhang, Yang Yang, Yanjie Guo, Yanhong Fan, Mingming Zhang, Wanrong Man, Erhe Gao, Wei Hu, Russel J Reiter, Haichang Wang, Dongdong Sun
Melatonin reportedly protects against several cardiovascular diseases including ischemia/reperfusion (I/R), atherosclerosis, and hypertension. The present study investigated the effects and mechanisms of melatonin on cardiomyocyte autophagy, apoptosis, and mitochondrial injury in the context of myocardial infarction (MI). We demonstrated that melatonin significantly alleviated cardiac dysfunction after MI. Four weeks after MI, echocardiography and Masson staining indicated that melatonin notably mitigated adverse left ventricle remodeling...
January 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/27680548/mst1-inhibits-cmecs-autophagy-and-participates-in-the-development-of-diabetic-coronary-microvascular-dysfunction
#14
Jie Lin, Lei Zhang, Mingming Zhang, Jianqiang Hu, Tingting Wang, Yu Duan, Wanrong Man, Bin Wu, Jiaxu Feng, Lei Sun, Congye Li, Rongqing Zhang, Haichang Wang, Dongdong Sun
Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice. Diabetic Mst1 transgenic mice exhibited impaired cardiac microvessel integrity and decreased cardiac function...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27661120/frmd6-inhibits-human-glioblastoma-growth-and-progression-by-negatively-regulating-activity-of-receptor-tyrosine-kinases
#15
Yin Xu, Kaiqiang Wang, Qin Yu
FRMD6 is an Ezrin/Radixin/Moesin (ERM) family protein and a human homologue of Drosophila expanded (ex). Ex functions in parallel of Drosophila merlin at upstream of the Hippo signaling pathway that controls proliferation, apoptosis, tissue regeneration, and tumorigenesis. Even though the core kinase cascade (MST1/2-Lats1/2-YAP/TAZ) of the Hippo pathway has been well established, its upstream regulators are not well understood. Merlin promotes activation of the Hippo pathway. However, the effect of FRMD6 on the Hippo pathway is controversial...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27618557/mst1-mst2-protein-kinases-regulation-and-physiologic-roles
#16
REVIEW
Jacob A Galan, Joseph Avruch
The MST1 and MST2 protein kinases comprise the GCK-II subfamily of protein kinases. In addition to their amino-terminal kinase catalytic domain, related to that of the Saccharomyces cerevisiae protein kinase Ste20, their most characteristic feature is the presence near the carboxy terminus of a unique helical structure called a SARAH domain; this segment allows MST1/MST2 to homodimerize and to heterodimerize with the other polypeptides that contain SARAH domains, the noncatalytic polypeptides RASSF1-6 and Sav1/WW45...
October 4, 2016: Biochemistry
https://www.readbyqxmd.com/read/27560370/hras-helps-hippo-heterodimerize-to-evade-tumor-suppression
#17
Daniela Araiza-Olivera, Jonathan Chernoff
Ras oncoproteins can promote or suppress cellular apoptosis, but the mechanisms underlying these varied responses remain incompletely understood. Ras is linked to the Hippo tumor suppressor pathway, a highly conserved signaling cassette that regulates organ size in animals ranging from flies to humans. The proximal members of this pathway, Mammalian Ste20-like kinases (Msts) -1 and -2, self-associate in homodimers and also form heterodimers with other proteins. Formation of such complexes is known to regulate Mst kinase activity and thus, the Hippo pathway...
August 25, 2016: Small GTPases
https://www.readbyqxmd.com/read/27535619/pharmacological-targeting-of-kinases-mst1-and-mst2-augments-tissue-repair-and-regeneration
#18
Fuqin Fan, Zhixiang He, Lu-Lu Kong, Qinghua Chen, Quan Yuan, Shihao Zhang, Jinjin Ye, Hao Liu, Xiufeng Sun, Jing Geng, Lunzhi Yuan, Lixin Hong, Chen Xiao, Weiji Zhang, Xihuan Sun, Yunzhan Li, Ping Wang, Lihong Huang, Xinrui Wu, Zhiliang Ji, Qiao Wu, Ning-Shao Xia, Nathanael S Gray, Lanfen Chen, Cai-Hong Yun, Xianming Deng, Dawang Zhou
Tissue repair and regenerative medicine address the important medical needs to replace damaged tissue with functional tissue. Most regenerative medicine strategies have focused on delivering biomaterials and cells, yet there is the untapped potential for drug-induced regeneration with good specificity and safety profiles. The Hippo pathway is a key regulator of organ size and regeneration by inhibiting cell proliferation and promoting apoptosis. Kinases MST1 and MST2 (MST1/2), the mammalian Hippo orthologs, are central components of this pathway and are, therefore, strong target candidates for pharmacologically induced tissue regeneration...
August 17, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27527217/unveiling-hidden-dynamics-of-hippo-signalling-a-systems-analysis
#19
Sung-Young Shin, Lan K Nguyen
The Hippo signalling pathway has recently emerged as an important regulator of cell apoptosis and proliferation with significant implications in human diseases. In mammals, the pathway contains the core kinases MST1/2, which phosphorylate and activate LATS1/2 kinases. The pro-apoptotic function of the MST/LATS signalling axis was previously linked to the Akt and ERK MAPK pathways, demonstrating that the Hippo pathway does not act alone but crosstalks with other signalling pathways to coordinate network dynamics and cellular outcomes...
2016: Genes
https://www.readbyqxmd.com/read/27510910/mst1-coordinately-regulates-autophagy-and-apoptosis-in-diabetic-cardiomyopathy-in-mice
#20
Mingming Zhang, Lei Zhang, Jianqiang Hu, Jie Lin, Tingting Wang, Yu Duan, Wanrong Man, Jiaxu Feng, Lei Sun, Hongbing Jia, Congye Li, Rongqing Zhang, Haichang Wang, Dongdong Sun
AIMS/HYPOTHESIS: Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM. METHODS: Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes...
November 2016: Diabetologia
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