Functional analysis of an atypical nuclear small GTPase in the oncogenic signal

非典型核小 GTP 酶在致癌信号中的功能分析

• 批准号: 23570166
• 负责人: TAGO Kenji
• 金额: $ 3.41万
• 依托单位: Jichi Medical University (2012-2013)Nara Institute of Science and Technology (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23570166/
• 关键词: シグナル伝達; 発がんシグナル; Gタンパク質; 低分子量G蛋白質; シグナル伝達系

kappaB-Ras is a nuclear-cytoplasmic GTPase that mainly present as GTP-bound form with no stimulating conditions, and its cellular localization is regulated by its bound guanine nucleotides. Here, we found that kappaB-Ras is essential for Ras (G12V)-induced tumorigenesis, although kappaB-Ras itself lacks the oncogenic activities. To clarify the mechanism, by which kappaB-Ras is involved in Ras (G12V)-caused tumorigenesis, we purified the protein complexes including kappaB-Ras2, and identified novel interacting proteins of kappaB-Ras, such as TRB3 and DDB1. TRB3 exhibited the tumor suppressive activity against Ras (G12V). Furthermore, TRB3 induced SUMOylation of kappaB-Ras, and this seems to cause the inhibition of Ras (G12V)-induced transformation. These observations suggest that kappaB-Ras harbors the critical roles in tumorigenesis induced by oncogenic Ras, and this is most likely to be regulated by novel tumor suppressor TRB3 through the SUMOylation of kappaB-Ras.

kappaB-Ras是一种主要以GTP结合形式存在的核质型GTP酶，其细胞定位受其结合的鸟嘌呤核苷酸调节。在这里，我们发现kappaB-Ras是Ras（G12 V）诱导的肿瘤发生所必需的，尽管kappaB-Ras本身缺乏致癌活性。为了阐明kappaB-Ras参与Ras（G12 V）引起的肿瘤发生的机制，我们纯化了包括kappaB-Ras 2的蛋白复合物，并鉴定了新的kappaB-Ras相互作用蛋白，如TRB 3和DDB 1。TRB 3对Ras（G12 V）表现出肿瘤抑制活性。此外，TRB 3诱导kappaB-Ras的SUMO化，并且这似乎导致Ras（G12 V）诱导的转化的抑制。这些观察结果表明，kappaB-Ras在致癌Ras诱导的肿瘤发生中具有关键作用，并且这最有可能是由新的肿瘤抑制因子TRB 3通过kappaB-Ras的SUMO化来调节的。

项目成果

Aurora kinase A critically contributes to the resistance to anti‐cancer drug cisplatin in JAK2 V617F mutant‐induced transformed cells

• DOI: 10.1016/j.febslet.2011.04.068
• 发表时间: 2011-06
• 期刊: FEBS Letters
• 影响因子: 3.5
• 作者: K. Sumi;K. Tago;T. Kasahara;M. Funakoshi-Tago

Rab33a Mediates Anterograde Vesicular Transport for Membrane Exocytosis and Axon Outgrowth

• DOI: 10.1523/jneurosci.0989-12.2012
• 发表时间: 2012-09-12
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Nakazawa, Hitomi;Sada, Tadayuki;Inagaki, Naoyuki
• 通讯作者: Inagaki, Naoyuki

Critical role of FANCC in JAK2 V617F mutant-induced resistance to DNA cross-linking drugs.

FANCC 在 JAK2 V617F 突变体诱导的 DNA 交联药物耐药性中发挥关键作用。

• DOI: 10.1016/j.cellsig.2013.07.003
• 发表时间: 2013
• 期刊: Cell Signal
• 影响因子: 4.8
• 作者: Ueda F;Sumi K;Tago K;Kasahara T;Funakoshi-Tago M
• 通讯作者: Funakoshi-Tago M

Phosphorylation of doublecortin by protein kinase A orchestrates microtubule and actin dynamics to promote neuronal progenitor cell migration

蛋白激酶 A 磷酸化双皮质素协调微管和肌动蛋白动力学，促进神经元祖细胞迁移

• 发表时间: 2012
• 期刊: J Biol Chem
• 影响因子: 4.8
• 作者: Toriyama M;Mizuno N;Fukami T;Iguchi T;Toriyama M;Tago K;Itoh H
• 通讯作者: Itoh H

細胞のがん化におけるIL-33の役割の解析

IL-33在细胞癌变中的作用分析

• 发表时间: 2012
• 作者: 太田聡;多胡憲治;多胡めぐみ;松儀実広;柳澤健
• 通讯作者: 柳澤健