轉譯後修飾作用
(post-translational modifications) 包含甲基化
(methylation)、磷酸化
(phosphorylation)、泛素化
(ubiquitination)、類小泛素
化修飾
(sumoylation) 等。過去有研究指出類小泛素化修飾可以調節目標蛋白
質的穩定度，進而調節許多細胞內反應，例如：細胞核運輸作用、
DNA 複
製、調節轉錄作用、染色體分離、訊息傳遞、細胞週期調控、DNA 修補作用等
現象。類小泛素化修飾是藉由一系列的酵素，使類小泛素這個蛋白質能夠修飾
目標蛋白質的
lysine
殘基。
類小泛素化修飾是一個可逆性動態修飾過程，類
小泛素化修飾連結途徑包含有三個主要的步驟：
活化 (activation)，結合
(conjugation)，連接 (ligation)，它們分別是藉由
E1、E2 和
E3 這三種不同的
酵素催化的。本篇研究主要是藉由類小泛素
E3 連接酶 PIAS1 進行修飾作用，
我們發現
Hairy and Enhancer of split 1 (Hes-1) 蛋白質可被類小泛素修飾。若
將類小泛素
E3 連接酶 PIAS1 突變，就無法讓野生型
Hes-1 進行類小泛素修
飾化，證實
PIAS1 的參與對於類小泛素化修飾扮演重要的角色。除此之外，
將類小泛素目標蛋白質
Hes-1 序列上第八個位置的
lysine 突變，會抑制
Hes-1 進行類小泛素化修飾。因此，透過
PIAS1 所進行的類小泛素化修飾可以
使目標蛋白質
Hes-1 蛋白質更為穩定。之後更進一步探討在空間學習與記憶
中，Hes-1 進行類小泛素化修飾與
GluR1 蛋白質表現的關係。實驗結果顯示，
Hes-1 進行類小泛素化修飾使空間學習與記憶變差並使
GluR1 蛋白質表現下
降。 / There are several post-translational modifications including methylation、
phosphorylation、ubiquitination、sumoylation, etc. Previously studies
indicated that sumoylation can regulate target protein stability. Sumoylation
also modulates many cellular processes, including nuclear transport, DNA
replication, transcription, chromosome segregation, signal transduction, cell
cycle and DNA repair. Sumoylation is a process mediated by SUMOs which
are attached to specific lysine residues of target proteins by the action of a
series of enzymes. Sumoylation is a dynamically reversible process.
Sumoylation consists of three steps：activation, conjugation and ligation,
which are respectively mediated by E1, E2 and E3 ligase. This study focuses
on SUMO modification by E3 ligase. Here, we identified a new target protein,
Hairy and Enhancer of split 1 (Hes-1), for SUMO conjugation. The E3 ligase
deficient mutant of PIAS1 that leads to failure of Hes-1 protein sumoylation.
We demonstrared that PIAS1 is involved in SUMO modification of Hes-1. In
addition mutantion of Hes-1 protein on lysine 8 residue that inhibits the
sumoylation of Hes-1. Therefore, sumoylation of Hes-1 regulates the protein
stability of Hes-1. Further study of the relationship between sumoylation of
Hes-1 and GluR1 in spatial memory formation indicated that spatial memory
is impaired and GluR1 protein expression is decreased upon sumoylation of
Hes-1.
| Identifer | oai:union.ndltd.org:CHENGCHI/G0099754005 |
| Creators | 許芳芸, Hsu, Fang Yun |
| Publisher | 國立政治大學 |
| Source Sets | National Chengchi University Libraries |
| Language | 中文 |
| Detected Language | English |
| Type | text |
| Rights | Copyright © nccu library on behalf of the copyright holders |
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