Regulating mechanism for intracellular stability of tyrosine hydroxylase and neurodegeneration

酪氨酸羟化酶细胞内稳定性与神经退行性变的调节机制

• 批准号: 22590946
• 负责人: NAKASHIMA Akira
• 金额: $ 1.91万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590946/
• 关键词: 神経分子病態学; パーキンソン病; チロシン水酸化酵素; 細胞内安定性; プロテアソーム分解; 14-3-3プロテイン; リン酸化; 細胞内安定性制御機構

We revealed that the phosphorylation of the N-terminal portion of tyrosine hydroxylase (TH) positively regulates the intracellular stability of the enzyme. The phosphorylation of two serine residues was shown to be a trigger for the proteasomedigestion. Moreover, 14-3-3 protein which is major protein in mammalian brain is a critical factor in regulating TH stability by acting to promote the degradation of TH phosphorylated at its N-terminus.

我们发现，酪氨酸羟化酶(TH)N末端部分的磷酸化正向调节了该酶的细胞内稳定性。两个丝氨酸残基的磷酸化被证明是蛋白酶消化的触发因素。此外，14-3-3蛋白是哺乳动物大脑中的主要蛋白质，通过促进N端磷酸化的TH的降解，是调节TH稳定性的关键因素。

项目成果

Intracellular degradation and localization of tyrosine hydroxylase : phosphorylation and proteasomal digestion of the enzyme

酪氨酸羟化酶的细胞内降解和定位：酶的磷酸化和蛋白酶体消化

• 发表时间: 2011
• 作者: Akira Nakashima;et al;他6名
• 通讯作者: 他6名

Intracellular degradation and localization of tyrosine hydroxylase

酪氨酸羟化酶的细胞内降解和定位

• 发表时间: 2012
• 作者: Akira Nakashima;et al;他5名
• 通讯作者: 他5名

Phosphorylation of the N-terminal portion of tyrosine hydroxylase triggers proteasomal digestion of the enzyme

• DOI: 10.1016/j.bbrc.2011.03.020
• 发表时间: 2011-04-08
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Nakashima, Akira;Mori, Keiji;Ota, Akira
• 通讯作者: Ota, Akira

Intracellular degradation and localization of tyrosine hydroxylase.

酪氨酸羟化酶的细胞内降解和定位。

• 发表时间: 2012
• 作者: Nakashima A;Mori K;Kaneko YS;Nagasaki N;Nagatsu T and Ota A.
• 通讯作者: Nagatsu T and Ota A.

Intracellular degradation and localization of tyrosine hydroxylase; phosphorylation and proteasomal digestion of the enzyme.

酪氨酸羟化酶的细胞内降解和定位；

• 发表时间: 2011
• 作者: Nakashima A;Mori K;Kaneko YS;Nagasaki H;Hayashi H;Nagatsu T and Ota A.
• 通讯作者: Nagatsu T and Ota A.