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Publications
Publications (27)
Protein methylesterase‐1 (PME‐1) is an essential enzyme that catalyzes the demethylation of protein phosphatases 2A (PP2A) and PP4 catalytic subunits to alter the composition of holoenzymes. Elevated PME‐1 protein levels are observed in neurodegenerative diseases and cancer, suggesting the involvement of dysregulation of PP2A/PP4 methylation. Howev...
Osteoclasts are specialized cells essential for bone resorption, a crucial process in bone remodeling, and dysregulation of osteoclastogenesis can lead to pathological bone loss such as osteoporosis and rheumatoid arthritis. Therefore, understanding the precise mechanisms governing osteoclast differentiation is crucial for developing effective ther...
Age‐related macular degeneration (AMD) is a leading cause of blindness in Western and developing countries. Since antivascular endothelial growth factor (VEGF) therapy is available for the regression of choroidal neovascularization (CNV), it does not work for the pathophysiology of AMD so a cure is increasingly demanded. Whale oil promotes various...
The ability of an organism to overcome infectious diseases has traditionally been linked to killing invading pathogens. Accumulating evidence, however, indicates that, apart from restricting pathogen loads, organismal survival is coupled to an additional yet poorly understood mechanism called disease tolerance. Here we report that p16 High immune c...
Background and Aims
Acute kidney injury caused by renal ischemia/reperfusion (I/R) is a major clinical problem in many aspects of urology fields such as kidney transplantation and partial nephrectomy, but there is no effective treatment. Linaclotide, a guanylate cyclase C agonist clinically approved as a laxative, has recently been shown to be reno...
Dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) protect against age-related macular degeneration (AMD). We here examined the effects of whale oil, which contains ω-3 LCPUFAs, in a mouse model of AMD. Mice were fed either a diet supplemented with whale oil or a control diet free of ω-3 LCPUFAs beginning 2 weeks before induction of choro...
The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity A...
The Omicron variant continuously evolves under the humoral immune pressure obtained by vaccination and SARS-CoV-2 infection and the resultant Omicron subvariants exhibit further immune evasion and antibody escape. Engineered ACE2 decoy composed of high-affinity ACE2 and IgG1 Fc domain is an alternative modality to neutralize SARS-CoV-2 and we previ...
Reports of post-acute COVID-19 syndrome, in which the inflammatory response persists even after SARS-CoV-2 has disappeared, are increasing ¹ , but the underlying mechanisms of post-acute COVID-19 syndrome remain unknown. Here, we show that SARS-CoV-2-infected cells trigger senescence-like cell-cycle arrest 2,3 in neighboring uninfected cells in a p...
Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studie...
Sezary syndrome is a rare type of non-Hodgkin lymphoma. Protein phosphatase 2A (PP2A) is an important tumor suppressor whose activity is widely inhibited in a variety of tumors. Recently, reactivation of PP2A has attracted increasing attention as a promising approach for cancer therapy. Phenothiazine anti-psychotic perphenazine (PPZ) exerts antitum...
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells with ability to self-replicate and differentiate into mesodermal derivatives, such as adipocytes and osteoblasts. BM-MSCs are a critical component of the tumor microenvironment. They support tumor progression by recruiting additional BM-MSCs and by differentiating into...
SET (also called I2PP2A and TIF-1) is a multi-functional protein that regulates a variety of cell signaling including nucleosome assembly, histone binding, and tumorigenesis. Elevated SET protein levels are observed in various human tumors, and are correlated with poor prognosis and drug-resistance. We recently reported that SET protein levels in c...
Osteosarcoma (OSA) is the most common bone tumor in dogs. Protein phosphatase 2A (PP2A), an evolutionary conserved serine/threonine protein phosphatase, is a crucial tumor suppressor. SET is a PP2A inhibitory protein that directly interacts with PP2A and suppresses its phosphatase activity. SET has been reported as a contributor of wide range of hu...
Excessive phosphorylation of intracellular proteins is one of the causes of the development and malignant progression of cancer. Not a few molecular-targeted anticancer drugs have been developed to inhibit abnormal activation of limited number of kinases. Therefore, novel drugs development from this point of view is now facing difficulty. On the ot...
Reversible methyl‐esterification (methylation) of Leu309 in the protein phosphatase 2A catalytic subunit (PP2Ac) is essential for proper biogenesis of the PP2A holoenzyme. Accumulating evidence links PP2Ac methylation to diseases, including cancer and neurodegenerative disorders. Protein phosphatase methyl‐esterase (PME‐1) specifically catalyzes PP...
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possesses the ability to self-renew and dedifferentiate. The...
Canine mammary tumor is the most common neoplasm in female dogs, and it has generated considerable attention as a translational model for human breast cancer. Ser/Thr protein phosphatase 2A (PP2A) plays a critical role as a tumor suppressor, and SET/I2PP2A, the endogenous inhibitory protein of PP2A, binds directly to PP2A and suppresses its phospha...
Tumor microenvironment has been implicated in tumor development and progression. As a three-dimensional tumor microenvironment model, air liquid interface (ALI) organoid culture from oncogene transgenic mouse gastrointestinal tissues was recently produced. However, ALI organoid culture system from tissues of colorectal cancer patients has not been...
Lymphoma is one of the most common malignant tumors in canine. Protein phosphatase 2A (PP2A), a well-conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. Perphenazine (PPZ) is one of the phenothiazines and widely used as an antipsychotic drug. Recently, it is reported that PPZ directly binds with scaffolding subunit...
Canine melanoma is one of the most important diseases in small animal medicine. Protein phosphatase 2A (PP2A), a well conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. SET/I2PP2A is an endogenous inhibitor for PP2A, which directly binds to PP2A and suppresses its phosphatase activity. Elevated SET protein levels h...