九州大学-研究者情報 [藤本景子 (助教) 薬学研究院臨床薬学部門]

1.	Keiko Fujimoto,Sanae Nakashima,Shotaro Uchida,Riham N S Amen,Yuji Ishii,Yuko Hirota,Yoshitaka Tanaka, HM1.24/BST-2 is constitutively poly-ubiquitinated at the N-terminal amino acid in the cytoplasmic domain , Biochemistry and Biophysics Reports, 10.1016/j.bbrep.2020.100784, 2020 Jul 20;23:100784., 2020.07.
2.	Fujimoto K,Uchida S,Amen RNS,Ishii Y,Tanaka Y,Hirota Y., Lysosomal integral membrane protein LGP85 (LIMP-2) is ubiquitinated at the N-terminal cytoplasmic domain., Biochemical and Biophysical Research Communications, 524, 2, 424-430, Epub 2020 Jan 30., 2020.04.
3.	藤本景子,井田広顕,廣田有子,石谷雅樹,天野潤,田中嘉孝, Intracellular Dynamics and Fate of a Humanized Anti-Interleukin-6 Receptor Monoclonal Antibody, Tocilizumab., Molecular Pharmacology, 10.1124, 88, 4, 660-675, 2015.10, Tocilizumab (TCZ), a humanized anti-interleukin-6 (IL-6) receptor (IL-6R) monoclonal antibody, abrogates signal transducer protein gp130-mediated IL-6 signaling by competitively inhibiting the binding of IL-6 to the receptor, and shows clinical efficacy in autoimmune and inflammatory diseases. Despite accumulating evidence for therapeutic efficacy, the behavior and fate of TCZ at the cellular level remain largely unknown. To address this, we evaluated the endocytosis and intracellular trafficking of IL-6R in HeLa cells. The results of our study provide evidence that IL-6R is constitutively internalized from the cell surface by ligand or TCZ binding and the expression of gp130 in an independent manner and is targeted via endosomes without being significantly directed to the recycling pathway to, and degraded in, lysosomes. Furthermore, the cytoplasmic tail of IL-6R is required for constitutive endocytosis of the receptor, which is mediated by the clathrin and AP-2 complex. We further demonstrate that FcRn, whose function is to regulate the serum persistence of IgG, is confined primarily to early/recycling endosomes and rapidly transits between these compartments and late endosomes/lysosomes without being degraded. Importantly, the expression of FcRn induces the segregation of TCZ from IL-6R, resulting in extensive colocalization of TCZ and FcRn in IL-6R-depleted endosomal compartments. Collectively, our results suggest that FcRn can accelerate the retrieval of the internalized TCZ, not only from endosomes but also from lysosomes. Our findings provide new insight into the mechanism by which the antibody internalized into cells is rescued from lysosomal degradation and into how its serum levels are maintained..
4.	Hideaki Fujita, Keiko Fujimoto, Kenzo Tokunaga, and Yoshitaka Tanaka, Intracellular logistics of BST-2/tetherin, Current HIV Research, in press, 2012.08.

主要学会発表等

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1.	Riham N.S. Amen,大澤みな,廣田有子,石井祐次,田中嘉孝,藤本景子, Flotillin-2 Regulates the Localization of Flotillin-1 to and within Late Endosomes/Lysosomes, 第39回日本薬学会九州山口支部大会, 2022.11.
2.	Riham Amen,Yoshitaka Tanaka,Yuko Hirota,Yuu Miyauchi,Yuji Ishii,Keiko Fujimoto, A proteomic analysis of integral and associated lysosomal membrane proteins, 第42回日本分子生物学会年会, 2019.12.
3.	Keiko Fujimoto,Ryo Tadakuma,Chiaki Tanaka,Yuko Hirota,Yuu Miyauchi,Yuji Ishii,Yoshitaka Tanaka., Papuamine prevents the fusion between autophagosomes and lysosomes by inhibiting the maturation of autophagosomes., Experimental Biology 2019, 2019.04.
4.	高原奈津美,宮内優,廣田有子,田中嘉孝,藤本景子, trans-Golgi network膜タンパク質TGN46のTGNからエンドソームへの輸送制御機構の解明, 第41回日本分子生物学会年会, 2018.11.
5.	多田隈凌,田中千晶,廣田有子,宮内優,田中嘉孝,藤本景子, 海綿由来アルカロイドpapuamineはオートファゴソームとリソソームの融合を阻害する, 第41回日本分子生物学会年会, 2018.11.
6.	藤本景子, 海綿由来アルカロイド papuamine によるオートファゴソーム成熟過程の分子制御機構, 平成30年度内外環境応答・代謝酵素研究会, 2018.11.
7.	藤本景子, 井田　広顕, 廣田有子, 石谷　雅樹, 天野　潤, 田中嘉孝, ヒト化抗インターロイキン-6 受容体モノクローナル抗体（トシリズマブ）の細胞内動態, 日本薬物動態学会第３１回年会, 2016.10.
8.	藤本景子, 廣田有子, 田中嘉孝, Trans-Golgi network膜タンパク質TGN46の局在と輸送を制御するユビキチン化機構の解析, 生体機能と創薬シンポジウム２０１３, 2013.08.
9.	藤本景子, 藤田英明, 廣田有子, 田中嘉孝, trans-Golgi network膜タンパク質TGN46のユビキチン化機構の解明, 第６５回日本細胞生物学会, 2013.06.
10.	藤本景子、吉永奈央、平井祥一、藤田英明、廣田有子、田中嘉孝, trans-Golgi network膜タンパク質 TGN46 の細胞内輸送および局在化の分子制御機構, 第84回日本生化学会大会, 2011.09.
11.	藤本景子、吉永奈央、平井祥一、廣田有子、静川直子、藤田英明、田中嘉孝, trans-Golgi network膜タンパク質TGN46の細胞内輸送および局在化の分子制御機構に関する研究, 第27回日本薬学会九州支部大会, 2010.12.