Functions of the Maf transcription factors in development and differentiation

Maf转录因子在发育和分化中的功能

• 批准号: 16590215
• 负责人: SAKAI Masaharu
• 金额: $ 1.92万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590215/
• 关键词: Chondrocyte; Cellular differentiation; Transcription factors; Maf; CTGF; GST-P; C; EBP; DNA micro-array; 標的遺伝子; ノックアウトマウス

1,c-Maf regulates CTGF gene ; We have previously reported that the c-Maf and MafB transcription factors were specifically expressed in the differentiation process of lens, cartilage, spinal cord and kidney. However the target genes and functions in these tissues are not known. Introduction of the Maf gene into the fibroblast cell line using adenovirus vector induced connective tissue growth factor (CTGF) gene, which has pivotal functions in cartilage development. From the detailed analyses, including EMSA, reporter transfection and ChIP analyses, c-Maf binds to the promoter region and 5'-untranslated regions of CTGF gene and strongly activates this gene. (Biochem Biophys Res Commn 339,1089-1097,2006)2.Identification of c-Maf target genes by DNA micro-array analysis : To identify the target genes of c-Maf, we have performed DNA micro-array analysis using the mouse embryonic fibroblast (MEF) cells from wild and c-maf knock-out mice. We identified several genes, including fibroblast growth factors (Fgf 18 and Fgf 9), which significantly reduced the expression in KO-MEF cells. The detailed analyses on these genes are currently in progress.3,Regulation of glutathione S-transferase (GST-P) gene during hepatocarcinogenesis. GST-P is a tumor marker activated by the Nrf2/MafK hetero-dimers in early stage of carcinogenesis (Biochemical J.380,515-521,2004). Recently, we identified the CAAT enhancer binding protein α (C/EBPα) as a suppressor of this gene in the normal liver. C/EBPα specifically binds to the GPE1,a strong enhancer element of GST-P gene, in vitro and in vivo. C/EBPα expressed in normal liver and strongly inhibited the Nrf2/MafK activity by competing the binding site (GPE1) with the Nrf2/MafK. In the early stage of carcinogenesis, the C/EBPα expression is completely shut-off, and the substitution of GPE1 binding factor from C/EBPα to the Nrf2/MafK lead to the strong induction of GST-P expression. (J.Biol.Chem.in press)

1、c-Maf调控CTGF基因；我们之前报道过c-Maf和MafB转录因子在晶状体、软骨、脊髓和肾脏的分化过程中特异表达，但在这些组织中的靶基因和功能是不同的。使用腺病毒载体诱导的结缔组织生长因子（CTGF）基因将 Maf 基因引入成纤维细胞系，该基因在软骨发育中具有关键功能，包括 EMSA、报告基因转染和。 ChIP分析，c-Maf与CTGF基因的启动子区和5'-非翻译区结合并强烈激活该基因(Biochem Biophys Res Commn 339,1089-1097,2006)2.通过DNA鉴定c-Maf靶基因。微阵列分析：为了鉴定 c-Maf 的靶基因，我们使用小鼠胚胎成纤维细胞 (MEF) 进行了 DNA 微阵列分析我们鉴定了一些基因，包括成纤维细胞生长因子（Fgf 18 和 Fgf 9），它们在 KO-MEF 细胞中的表达显着降低，目前正在进行对这些基因的详细分析。 3、肝癌发生过程中谷胱甘肽S-转移酶（GST-P）基因的调节 GST-P是由Nrf2/MafK异二聚体激活的肿瘤标志物。癌发生的早期阶段（Biochemical J.380,515-521,2004）最近，我们鉴定出 CAAT 增强子结合蛋白 α (C/EBPα) 作为该基因在正常肝脏中特异性结合的抑制剂。 GST-P 基因的强增强子元件，在体外和体内正常肝脏中表达，并通过竞争强烈抑制 Nrf2/MafK 活性。 Nrf2/MafK 的结合位点（GPE1）在癌变早期，C/EBPα 表达完全关闭，GPE1 结合因子从 C/EBPα 替换为 Nrf2/MafK 导致强癌变。 GST-P 表达的诱导（J.Biol.Chem.in press）

项目成果

CCAAT enhancer binding protein α(C/EBP α) suppresses the rat placental glutathione S-transferase gene in normal liver.

CCAAT 增强子结合蛋白 α(C/EBP α) 抑制正常肝脏中的大鼠胎盘谷胱甘肽 S-转移酶基因。

• 发表时间: 2006
• 期刊: J. Biol. Chem. (印刷中)
• 作者: Ikeda;H. et al.
• 通讯作者: H. et al.

Immunolocalization of cyclin D1 in the developing lens of c-maf -/- mice.

细胞周期蛋白 D1 在 c-maf -/- 小鼠发育晶状体中的免疫定位。

• 发表时间: 2006
• 期刊: Acta Histochem 107・6
• 作者: 山下英俊;山本禎子;Kitamei H.;Horie Y;Kase S;Kitamei H;Ikeda H;Kase S;KitameiH;Kase S
• 通讯作者: Kase S

Activation of connective tissue growth factor gene by the c-Maf and Lc-Maf transcription factors

• DOI: 10.1016/j.bbrc.2005.11.119
• 发表时间: 2006-01-27
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Omoteyama, K;Ikeda, H;Sakai, M
• 通讯作者: Sakai, M

Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis

• DOI: 10.1042/bj20031948
• 发表时间: 2004-06-01
• 期刊: BIOCHEMICAL JOURNAL
• 影响因子: 4.1
• 作者: Ikeda, H;Nishi, S;Sakai, M
• 通讯作者: Sakai, M

Expression of maf-B mRNA in the epithelium around the eyelid closure of the mouse eye at embryonic day 18.

胚胎第 18 天小鼠眼睑闭合周围上皮细胞中 maf-B mRNA 的表达。

• 发表时间: 2004
• 期刊: Anat Embryol 209・2
• 作者: Harada C;Harada T;Quah HM;Namekata K;Yoshida K;Ohno S;Tanaka K;Parada LF;Uchio E;Akahoshi M;Kaneko H;Kase S
• 通讯作者: Kase S