Mechanisms of cell growth and malignant transformation regulated by protein phosphorylation and dephosphorylation

蛋白质磷酸化和去磷酸化调控细胞生长和恶性转化的机制

基本信息

批准号：
12219201
负责人：
YAMAMOTO Tadashi
金额：
$ 149.57万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2004
项目状态：
已结题

项目摘要

We showed the followings through the studies on cell growth regulation with special interest in protein phosphorylation. 1. Tob (1) Tob functions as a tumor suppressor because #1: tob suppresses cell growth when overexpressed, #2: tob-deficient mice are prone to cancer, and #3: expression of tob mRNA is often suppressed in various human tumors. (2) Tob becomes phosphorylated by Erk1/2 upon growth factor stimulation, which results in the loss of anti-proliferative activity of Tob. (3) Tob participates in transcription regulation because #1: Tob associate with HDAC and suppresses transcription of the cyclin Dl gene, #2: Tob regulates BMP signaling through its interaction with Smads. Consequently, tob-deficient mice develop an osteopetrotic phenotype. #3: Tob complexes with the NOT transcription machinery that consists of at least 10 Cnot proteins (Cnot1-10). Among Cnot proteins Cnot7 interacts with RXRβ, and like RXRβ-deficient mice Cnot7-deficient mice are sterile because of Oligo-asthe … More no-teratozoospermia. (4) Tob shuttles between nucleus and cytoplasm. In the cytoplasm Tob associates with polyA binding protein and regulates translation of mRNA. 2. Tyosine phosphorylation (1) Cbl-c induces v-Src ubiquitination and degradation, and thereby suppresses v-Src-mediated malignant transformation. (2) Agonistic monoclonal antibody we produced activates receptor tyrosine kinase ALK on the surface of PC12 cells, and induces their proliferation and neuronal differentiation. (3) ALK utilizes SNT2 adaptor protein for cell signaling, which is relevant to malignant cell transformation by activated ALK. 3. M phase kinases (1) Overexpression of human homologs of drosophila tumor suppressor proteins LATS1/2 results in M phase arrest. (2) RNAi-mediated down-regulation of LATS2-interacting protein Ajuba induces inhibition of spindle formation and chromosome segregation. (3) Ajuba also negatively regulates Wnt signaling through its interaction with β-catenin. (4) Phosphorylation of chromokinesin Kid by Cdc2 is important for chromosome dynamics and M phase progression. These data contributes to deepening our understanding on cell growth regulation. Less

我们展示了对蛋白质磷酸菌的特殊兴趣的细胞生长调节的研究，因为＃1：TOB抑制过表达的细胞生长，＃2：TOB缺陷小鼠容易发生癌症，＃3 Subious人类肿瘤。因此，与SMAD相互作用。寡头……在细胞质和细胞质之间，更多的无翅目植物（4）与polya结合蛋白质的tob shottles（1）CBL-C诱导V-Src Ubiputination and Degrandations， V-SRC介导的恶性转化并通过激活的ALK诱导细胞转化CDC2的Chromokiness od对CDC2很重要

项目成果

期刊论文数量（305）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

TRAF6-deficient mice display hypohidrotic ectodermal dysplasia

DOI：
10.1073/pnas.132636999
发表时间：
2002-06-25
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Naito, A;Yoshida, H;Inoue, J
通讯作者：
Inoue, J

Tyrosine dephosphorylation and ethanol inhibition of NMDA receptor function

酪氨酸去磷酸化和乙醇抑制 NMDA 受体功能