Regulation of transcription factors by protein-protein interaction

通过蛋白质-蛋白质相互作用调节转录因子

• 批准号: 04454161
• 负责人: ISHII Shunsuke
• 金额: $ 3.9万
• 依托单位: The Institute of Physical & Chemical Research (RIKEN)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454161/
• 关键词: transcription factors; leucine zipper; inhibitor; 転写制御因子

Activity of many transcription factors are regulated by protein-protein interaction. We have investigated the regulation of transcription factors by protein-protein interaction. Especially, the following transcription factors that are involved in cellular growth control were focused.1. CRE(cAMP response element)-binding protein CRE-BP1.We previously indentified the CRE-binding protein CRE-BP1 by cDNA cloning. CRE-BP1 binds to CRE as a homodimer or heterodimer with c-Jun. We have indentified the CRE-BP1-related protein CRE-BPa by cDNA cloning. CRE-BPa forms a homodimer or a heterodimer with c-Jun or CRE-BP1, and binds to CRE.Interestingly, the trans-activating capacity of CRE-BPa was stimulated by TPA treatment.2. myb proto-oncogene product (Myb)We have found that the activity of Myb is negatively regulated by the leucine zipper motif located in the middle of Myb molecule. This suggests that an inhibitor binds to Myb through this leucien zipper and blocks its activity. We have identified two proteins, 90- and 130kDa proteins, that can bind to the Myb leucien zipper. We have also found that Myb can form a dimer through the leucine zipper and a Myb dimer cannot bind to DNA.This indicates that Myb itself also can function as an inhibitor.

许多转录因子的活性受蛋白质-蛋白质相互作用的调节。我们研究了蛋白质-蛋白质相互作用对转录因子的调节。特别关注了以下参与细胞生长控制的转录因子： 1． CRE（cAMP反应元件）结合蛋白CRE-BP1。我们之前通过cDNA克隆鉴定了CRE结合蛋白CRE-BP1。 CRE-BP1 以同二聚体或与 c-Jun 的异二聚体形式与 CRE 结合。我们通过cDNA克隆鉴定了CRE-BP1相关蛋白CRE-BPa。 CRE-BPa与c-Jun或CRE-BP1形成同二聚体或异二聚体，并与CRE结合。有趣的是，TPA处理刺激了CRE-BPa的反式激活能力。2． myb原癌基因产物（Myb）我们发现Myb的活性受到位于Myb分子中部的亮氨酸拉链基序的负调控。这表明抑制剂通过亮氨酸拉链与 Myb 结合并阻断其活性。我们已经鉴定出两种可以与 Myb leucien 拉链结合的蛋白质，即 90kDa 和 130kDa 蛋白质。我们还发现Myb可以通过亮氨酸拉链形成二聚体，而Myb二聚体不能与DNA结合。这表明Myb本身也可以起到抑制剂的作用。

项目成果

Nakagoshi,H.: "Functional domains of the human B-myb gene product." J.Biol.Chem.268,. 14161-14167 (1993)

Nakagoshi,H.：“人类 B-myb 基因产物的功能域。”

Tanikawa, J.: "Recognaition of spcific DNA sequences by the c-myb proto-oncogene product : role of three repeat units in the DNA-binding domain" Proc.Natl.Acad.Sci.U.S.A.90. 9320-9324 (1993)

Tanikawa, J.：“c-myb 原癌基因产物对特定 DNA 序列的识别：DNA 结合域中三个重复单元的作用”Proc.Natl.Acad.Sci.U.S.A.90。

Nomura,T.: "Negative autoregulation of c-Myb activity by homodimer formation through the leucine zipper." J.Biol.Chem.268,. 21914-21923 (1993)

Nomura,T.：“通过亮氨酸拉链形成同型二聚体，对 c-Myb 活性进行负向自动调节。”

Kanei-Ishii,C.: "Transactivation and transformation by Myb are negatively regulated by a leucine zipper structure" Proc.Natl.Acad.Sci.USA. 89. 3088-3092 (1992)

Kanei-Ishii,C.：“Myb 的反式激活和转化受到亮氨酸拉链结构的负调控”Proc.Natl.Acad.Sci.USA。

Nomura, N.: "Isolation and characterization of novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1" J.Biol.Chem.268. 21914-21923 (1993)

Nomura, N.：“编码 cAMP 反应元件结合蛋白 CRE-BP1 的基因家族新成员的分离和表征”J.Biol.Chem.268。