Development of therapeutic ways targeting molecular chaperones and ets transcription factors

开发针对分子伴侣和 ets 转录因子的治疗方法

• 批准号: 14370748
• 负责人: KAI Hirofumi
• 金额: $ 8.77万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370748/
• 关键词: CFTR; molecular chaperone; calnexin; calreticulin; MEF; lysozyme; PML nuclear body; ETS transcription factor; ガン; Heat Shock Protein; 分子シャペロン; vitamin K; heat shock protein

1.CFTR was exported from the ER to cis-Golgi and early endosome, suggesting that CFTR transport in the early secretory pathway may utilize a non-conventional pathway. This CFTR trafficking pathway may be a target for pharmacological modulation that selectively stimulates CFTR transport.2.Curcumin may have an unique effect as an accelerator of CFTR trafficking by decreasing calreticulin, a negative regulator of CFTR and have important implications in developing therapeutic approaches that target the trafficking of CFTR.3.The recruitment of MEF to PML nuclear bodies regulates lysozyme transcription in epithelial cells.4.MEF may play an important role in regulating HBD2 expression in epithelial cells.5.MEF is a tumor suppressor gene on the X chromosome with activities that are opposite to those of ETS-2.6.PML stimulated MEF transcriptional activity, resulting in the up-regulation of endogenous HBD 2 expression.

1.cftr从内质网输出到顺式高尔基体和早期内吞体内，提示cftr在早期分泌途径中可能通过非常规途径转运。2.姜黄素可能通过减少CFTR的负调控因子钙网蛋白而作为CFTR转运的加速器发挥独特的作用，并在开发针对CFTR3的治疗方法方面具有重要意义。3.MEF向PML核体募集调节上皮细胞中溶菌酶的转录。4.MEF可能在调节上皮细胞中HBD2的表达中发挥重要作用。5.MEF是X染色体上的一个肿瘤抑制基因，其活性与ETS-2.6相反。PML刺激MEF转录活性，导致内源性HBD2表达上调。

项目成果

Characterization of the trafficking pathway of cystic fibrosis transmembrane conductance regulator in baby hamster kidney cells.

小仓鼠肾细胞囊性纤维化跨膜电导调节因子运输途径的表征。

• 发表时间: 2004
• 期刊: J.Pharmacol.Sci. 95
• 作者: T.Okiyoneda;K.Harada;K.Yamahira;I.Wada;Y.Hashimoto;K.Ueno;M.A.Suico;T.Shuto;H.Kai
• 通讯作者: H.Kai

H.Jono.: "TGF-b-Smad signaling pathway negatively regulates nontypeable haemophilus influenzae-induced MUC5AC Mucin transcription via MAPK phosphatase-l-dependent inhibition of p38 MAPK"J.Biol.Chem.. 278. 27811-27819 (2003)

H.Jono.：“TGF-b-Smad 信号通路通过 p38 MAPK 的 MAPK 磷酸酶-1 依赖性抑制来负调节不可分型流感嗜血杆菌诱导的 MUC5AC 粘蛋白转录”J.Biol.Chem.. 278. 27811-27819 (2003)

Shuto T, Imasato A, Jono H et al.: "Glucocorticoids synergistically enhance nontypeable Haemophilus nfluenzae"J Biol Chem. 277. 17263-17270 (2002)

Shuto T、Imasato A、Jono H 等人：“糖皮质激素可协同增强不可分型的流感嗜血杆菌”J Biol Chem。

Sp1-dependent regulation of Myeloid Elf-1 like factor in human epithelial cells

• DOI: 10.1016/j.febslet.2005.04.015
• 发表时间: 2005-05-23
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Koga, T;Suico, MA;Kai, H
• 通讯作者: Kai, H

The ETS transcription factor MEF is a candidate tumor suppressor gene on the X chromosome

ETS转录因子MEF是X染色体上的候选抑癌基因

• 发表时间: 2002
• 期刊: Cancer Res 62
• 作者: Y.Seki;M.-A.Suico;A.Uto;A.Hisatsune;T.Shuto;Y.Isohama;H.Kai
• 通讯作者: H.Kai