在非应激细胞中，JNK靶向p53的泛素化和降解。
JNK targets p53 ubiquitination and degradation in nonstressed cells.
作者信息
Fuchs S Y, Adler V, Buschmann T, Yin Z, Wu X, Jones S N, Ronai Z
机构信息
The Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
出版信息
Genes Dev. 1998 Sep 1;12(17):2658-63. doi: 10.1101/gad.12.17.2658.
Abstract
In this study we elucidated the role of nonactive JNK in regulating p53 stability. The amount of p53-JNK complex was inversely correlated with p53 level. A peptide corresponding to the JNK binding site on p53 efficiently blocked ubiquitination of p53. Similarly, p53 lacking the JNK binding site exhibits a longer half-life than p53(wt). Outcompeting JNK association with p53 increased the level of p53, whereas overexpression of a phosphorylation mutant form of JNK inhibited p53 accumulation. JNK-p53 and Mdm2-p53 complexes were preferentially found in G0/G1 and S/G2M phases of the cell cycle, respectively. Altogether, these data indicate that JNK is an Mdm2-independent regulator of p53 stability in nonstressed cells.
摘要
在本研究中，我们阐明了非活性JNK在调节p53稳定性中的作用。p53-JNK复合物的量与p53水平呈负相关。与p53上JNK结合位点对应的肽有效地阻断了p53的泛素化。同样，缺乏JNK结合位点的p53比野生型p53具有更长的半衰期。与p53竞争结合JNK会增加p53的水平，而JNK磷酸化突变体形式的过表达则抑制p53的积累。JNK-p53和Mdm2-p53复合物分别优先在细胞周期的G0/G1期和S/G2M期被发现。总之，这些数据表明JNK是未受应激细胞中p53稳定性的一种不依赖Mdm2的调节因子。
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本文引用的文献
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Mdm2 association with p53 targets its ubiquitination.Mdm2与p53的结合使其发生泛素化。
Oncogene. 1998 Nov 12;17(19):2543-7. doi: 10.1038/sj.onc.1202200.
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MEKK1/JNK signaling stabilizes and activates p53.丝裂原活化蛋白激酶激酶1/应激活化蛋白激酶信号通路使p53稳定并激活。
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