Analysis of Functions and Domains of A Novel Cell Proliferation Relating Protein Meu-2

新型细胞增殖相关蛋白Meu-2的功能和结构域分析

• 批准号: 14580705
• 负责人: TSUNEOKA Makoto
• 金额: $ 1.92万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580705/
• 关键词: cell proliferation; nuclear protein; oncogene; myc; mina53; JmjC domain; gene expression; cell cycle; JmjCドメイン; 転写因子; マイクロアレイ; Mina53; がん

Myc is a ubiquitous mediator of cell proliferation and transactivates the expressions of genes through E-box sites. Although much effort has been made to investigate myc, myc still remains enigmatic, and information about additional genes controlled by myc can help elucidate the function of Myc.We found a novel gene, mina53 (myc-induced nuclear antigen with a MW of 53 kDa). The changes of the expression level of mina53 followed those of c-myc in various types of cells. When, c-Myc in the c-MycER chimeric protein was activated, mina53 mRNA was increased, even in the presence of an inhibitor for protein synthesis. c-Myc protein bound to the mina53 promoter region in vivo. The gene expression from the mina53 promoter was elevated by c-Myc through an E-box site in the mina53 promoter. Specific inhibition of mina53 expression by an RNA interference method severely suppressed cell proliferation. These results indicate that mina53 is a direct target gene of Myc, and suggest that mina53 is involved in mammalian cell proliferation.We generated a specific monoclonal anti-human Mina53 antibody and found that colon tumor cell lines expressed Mina53 highly. Then, we studied the expression of Mina53 in colon cancer to examine its possible role in carcinogenesis. Tissue sections of adenocarcinoma were stained immunohistochemically, and the expression of Mina53 was found to be elevated in all the adenocarcinomas compared to adjacent non-neoplastic tissues. Mina53 was expressed in all pathological grades of cancer as well as in the adenoma. Staining patterns of Ki-67, a biomarker for cell proliferation, were similar to those of Mina53 in most cases. While anti-Ki-67 antibody strongly stained cells in lymphoid germinal centers, however, antibody to Mina53 rarely stained those cells. Together, our results indicate that the elevated expression of Mina53 is a characteristic feature in colon cancer, one that may have therapeutic applications.

Myc是细胞增殖的普遍介质，并通过E-box位点反式激活基因的表达。尽管对myc的研究已经取得了很大进展，但myc仍然是一个谜，关于myc控制的其他基因的信息有助于阐明Myc的功能。mina 53在不同类型细胞中表达水平的变化与c-myc的变化相一致。当c-MycER嵌合蛋白中的c-Myc被激活时，即使在蛋白质合成抑制剂存在下，mina 53 mRNA也增加。c-Myc蛋白在体内与mina 53启动子区结合。通过mina 53启动子中的E-box位点，c-Myc提高了mina 53启动子的基因表达。通过RNA干扰方法特异性抑制mina 53表达严重抑制了细胞增殖。这些结果表明mina 53是Myc的直接靶基因，提示mina 53参与了哺乳动物细胞的增殖。然后，我们研究了Mina 53在结肠癌中的表达，以研究其在癌变中的可能作用。腺癌的组织切片进行化学染色，发现Mina 53的表达在所有腺癌中与相邻的非肿瘤组织相比都升高。Mina 53在所有病理级别的癌症以及在腺瘤中表达。Ki-67（细胞增殖的生物标志物）的染色模式在大多数情况下与Mina 53的染色模式相似。虽然抗Ki-67抗体强烈染色淋巴生发中心的细胞，然而，Mina 53抗体很少染色这些细胞。总之，我们的结果表明Mina 53的表达升高是结肠癌的一个特征，可能具有治疗应用。

项目成果

Amano S., Yamagishi S., Koda Y., Tuneoka M., Soejima M., Okamoto T., Inagaki Y., Yamada K., Kimura H.: "Polymorphisms of sorbitol dehydrogenase (SDH) gene and susceptibility to diabetic retinopathy."Med.Hypothesis. 60. 550-551 (2003)

Amano S.、Yamagishi S.、Koda Y.、Tuneoka M.、Soejima M.、Okamoto T.、Inagaki Y.、Yamada K.、Kimura H.：“山梨醇脱氢酶 (SDH) 基因的多态性与糖尿病视网膜病变的易感性

Teye K., Quaye I.K.E., Koda Y., Soejima M., Tsuneoka M., Pang H., Ekem I., Amoah A., G.B., Adjei A., Kimura H.: "A-61C and C-101G Hp gene promoter polymorphisms are respectively associated with ahaptoglobinemia and hypohaptoglobinemia in Ghana."Clin.Genet

Teye K.、Quaye I.K.E.、Koda Y.、Soejima M.、Tsuneoka M.、Pang H.、Ekem I.、Amoah A.、G.B.、Adjei A.、Kimura H.：“A-61C 和 C-101G Hp

Tsuneoka M., Umata T., Kimura H., Kod Y., Nakajima M., Kosai K., Takahashi T., Yamamoto A.: "c-myc induces autophagy in rat fibroblast cells."Cell Structure and Function. 28. 195-204 (2003)

Tsuneoka M.、Umata T.、Kimura H.、Kod Y.、Nakajima M.、Kosai K.、Takahashi T.、Yamamoto A.：“c-myc 诱导大鼠成纤维细胞自噬。”细胞结构和功能。

Tsuneoka M., Umata T., Kimura H., Koda Y., Nakajima M., Kosai K., Takahashi T., Yamamoto A.: "c-myc induces autophagy in rat fibroblast cells."Cell Structure and Function. 28. 195-204 (2003)

Tsuneoka M.、Umata T.、Kimura H.、Koda Y.、Nakajima M.、Kosai K.、Takahashi T.、Yamamoto A.：“c-myc 诱导大鼠成纤维细胞自噬。”细胞结构和功能。

Teye K., Quaye I.K.E., Koda Y., Soejima M., Pang H., Tsuneoka M., Amoah A.G.B., Adjei A., Kimura H.: "A novel I247T missense mutation in the haptoglobin 2 β chain decreases the protein expression and associates with ahaptoglobinemia"Human Genetics. 114. 4

Teye K.、Quaye I.K.E.、Koda Y.、Soejima M.、Pang H.、Tsuneoka M.、Amoah A.G.B.、Adjei A.、Kimura H.：“触珠蛋白 2 β 链中的一种新型 I247T 错义突变降低了蛋白质表达并与结合珠蛋白血症相关“人类遗传学。114. 4