@article{sai_nakanishi_scofield_tokarz_linder_cohen_ninomiya-tsuji_2023, title={Aberrantly activated TAK1 links neuroinflammation and neuronal loss in Alzheimer?s disease mouse models}, volume={136}, ISSN={["1477-9137"]}, url={http://dx.doi.org/10.1242/jcs.260102}, DOI={10.1242/jcs.260102}, abstractNote={ABSTRACT}, number={6}, journal={JOURNAL OF CELL SCIENCE}, publisher={The Company of Biologists}, author={Sai, Kazuhito and Nakanishi, Aoi and Scofield, Kimberly M. and Tokarz, Debra A. and Linder, Keith E. and Cohen, Todd J. and Ninomiya-Tsuji, Jun}, year={2023}, month={Mar} }
 @article{lopez-perez_sai_sakamachi_parsons_kathariou_ninomiya-tsuji_2021, title={TAK1 inhibition elicits mitochondrial ROS to block intracellular bacterial colonization}, volume={118}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.2023647118}, abstractNote={Significance}, number={25}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Lopez-Perez, Wilfred and Sai, Kazuhito and Sakamachi, Yosuke and Parsons, Cameron and Kathariou, Sophia and Ninomiya-Tsuji, Jun}, year={2021}, month={Jun} }
 @article{sai_parsons_house_kathariou_ninomiya-tsuji_2019, title={Necroptosis mediators RIPK3 and MLKL suppress intracellular Listeria replication independently of host cell killing}, volume={218}, ISSN={["1540-8140"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85067213651&partnerID=MN8TOARS}, DOI={10.1083/jcb.201810014}, abstractNote={RIPK3, a key mediator of necroptosis, has been implicated in the host defense against viral infection primary in immune cells. However, gene expression analysis revealed that RIPK3 is abundantly expressed not only in immune organs but also in the gastrointestinal tract, particularly in the small intestine. We found that orally inoculated Listeria monocytogenes, a bacterial foodborne pathogen, efficiently spread and caused systemic infection in Ripk3-deficient mice while almost no dissemination was observed in wild-type mice. Listeria infection activated the RIPK3-MLKL pathway in cultured cells, which resulted in suppression of intracellular replication of Listeria. Surprisingly, Listeria infection–induced phosphorylation of MLKL did not result in host cell killing. We found that MLKL directly binds to Listeria and inhibits their replication in the cytosol. Our findings have revealed a novel functional role of the RIPK3-MLKL pathway in nonimmune cell-derived host defense against Listeria invasion, which is mediated through cell death–independent mechanisms.}, number={6}, journal={JOURNAL OF CELL BIOLOGY}, publisher={Rockefeller University Press}, author={Sai, Kazuhito and Parsons, Cameron and House, John S. and Kathariou, Sophia and Ninomiya-Tsuji, Jun}, year={2019}, month={Jun}, pages={1994–2005} }
 @article{morioka_sai_omori_ikeda_matsumoto_ninomiya-tsuji_2016, title={TAK1 regulates hepatic lipid homeostasis through SREBP}, volume={35}, ISSN={["1476-5594"]}, DOI={10.1038/onc.2015.453}, abstractNote={Sterol-regulatory element-binding proteins (SREBPs) are key transcription factors regulating cholesterol and fatty acid biosynthesis. SREBP activity is tightly regulated to maintain lipid homeostasis, and is modulated upon extracellular stimuli such as growth factors. While the homeostatic SREBP regulation is well studied, stimuli-dependent regulatory mechanisms are still elusive. Here we demonstrate that SREBPs are regulated by a previously uncharacterized mechanism through transforming growth factor-β activated kinase 1 (TAK1), a signaling molecule of inflammation. We found that TAK1 binds to and inhibits mature forms of SREBPs. In an in vivo setting, hepatocyte-specific Tak1 deletion upregulates liver lipid deposition and lipogenic enzymes in the mouse model. Furthermore, hepatic Tak1 deficiency causes steatosis pathologies including elevated blood triglyceride and cholesterol levels, which are established risk factors for the development of hepatocellular carcinoma (HCC) and are indeed correlated with Tak1-deficiency-induced HCC development. Pharmacological inhibition of SREBPs alleviated the steatosis and reduced the expression level of the HCC marker gene in the Tak1-deficient liver. Thus, TAK1 regulation of SREBP critically contributes to the maintenance of liver homeostasis to prevent steatosis, which is a potentially important mechanism to prevent HCC development.}, number={29}, journal={ONCOGENE}, author={Morioka, S. and Sai, K. and Omori, E. and Ikeda, Y. and Matsumoto, K. and Ninomiya-Tsuji, J.}, year={2016}, month={Jul}, pages={3829–3838} }