Molecular mechanism underlying selective autophagy of aggregated protein

聚集蛋白选择性自噬的分子机制

• 批准号: 21700398
• 负责人: MATSUMOTO Gen
• 金额: $ 2.83万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21700398/
• 关键词: オートファジー; p62; タンパク質分解; シクエストソーム; ユビキチン; SQSTM1; ポリユビキチン; オートファゴソーム; アグリソーム

The specific phosphorylation of p62 in its ubiquitin-associated (UBA) domain, regulates the autophagic clearance of polyubiquitinated protein aggregate. This phosphorylated form of p62 binds to polyubiquitin chains with higher affinity, resulting in the efficient recruitment of polyubiquitinated proteins in the "sequestosomes" which are units of autophagosome entry. The phosphorylation in p62 regulates autophagic clearance of ubiquitinated proteins that are poorly degraded by proteasomes.

p62在其泛素相关（乌巴）结构域的特异性磷酸化调节多聚泛素化蛋白聚集体的自噬清除。这种磷酸化形式的p62以更高的亲和力与多聚泛素链结合，导致多聚泛素化蛋白质在作为自噬体进入单元的“隔离体”中的有效募集。p62的磷酸化调节蛋白酶体降解差的泛素化蛋白的自噬清除。

项目成果

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Novel gene therapy for polyglutamine diseases to degrade selectively the pathogenic protein

用于治疗多聚谷氨酰胺疾病的新型基因疗法，选择性降解致病蛋白

• 期刊: Nat.Biotech. (in press)
• 作者: Bauer;P.O.et al.
• 通讯作者: P.O.et al.

Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein

• DOI: 10.1038/nbt.1608
• 发表时间: 2010-03-01
• 期刊: NATURE BIOTECHNOLOGY
• 影响因子: 46.9
• 作者: Bauer, Peter O.;Goswami, Anand;Nukina, Nobuyuki
• 通讯作者: Nukina, Nobuyuki

Phosphorylation at p62/SQSTM1 promotes selective autophagy of ubiquitinated protein

p62/SQSTM1 磷酸化促进泛素化蛋白的选择性自噬

• 发表时间: 2009
• 作者: Sakai S;et.al.;Gen Matsumoto
• 通讯作者: Gen Matsumoto

Cross-Seeding Fibrillation of Q/N-Rich Proteins Offers New Pathomechanism of Polyglutamine Diseases

• DOI: 10.1523/jneurosci.0783-09.2009
• 发表时间: 2009-04-22
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Furukawa, Yoshiaki;Kaneko, Kumi;Nukina, Nobuyuki
• 通讯作者: Nukina, Nobuyuki