PDSM, a motif for phosphorylation-dependent SUMO modification

PDSM, a motif for phosphorylation-dependent SUMO modification
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DOI:
10.1073/pnas.0503698102
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发表时间:
2006-01-03
影响因子:
11.1
通讯作者:
Sistonen, L
Sistonen, L
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hietakangas, V;Anckar, J;Sistonen, L

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SUMO(小泛素样修饰剂)修饰调节许多细胞过程,包括转录。尽管苏酰化通常发生在共有四肽 Psi KxE 内的特定赖氨酸上,但其他修饰(例如磷酸化)可能会调节底物的苏酰化。我们发现了 PDSM(磷酸化依赖性苏酰化基序),由一个 SUMO 共有位点和一个相邻的脯氨酸定向磷酸化位点 (Psi KxExxSP) 组成。这个高度保守的基序调节多种底物的磷酸化依赖性苏酰化,例如热休克因子 (HSF)、GATA-1 和肌细胞增强因子 2。事实上,大多数含有 PDSM 的蛋白质都是转录调节因子。在 HSF 家族中,PDSM 在两个功能不同的成员 HSF1 和 HSF4b 之间是保守的,它们的反式激活能力通过磷酸化依赖性苏酰化受到抑制。作为除共有四肽之外的第一个经常出现的 SUMO 化决定簇,PDSM 为预测新的 SUMO 底物提供了有价值的工具。
SUMO (small ubiquitin-like modifier) modification regulates many cellular processes, including transcription. Although sumoylation often occurs on specific lysines within the consensus tetrapeptide Psi KxE, other modifications, such as phosphorylation, may regulate the sumoylation of a substrate. We have discovered PDSM (phosphorylation-dependent sumoylation motif), composed of a SUMO consensus site and an adjacent proline-directed phosphorylation site (Psi KxExxSP). The highly conserved motif regulates phosphorylation-dependent sumoylation of multiple substrates, such as heat-shock factors (HSFs), GATA-1, and myocyte enhancer factor 2. In fact, the majority of the PDSM-containing proteins are transcriptional regulators. Within the HSF family, PDSM is conserved between two functionally distinct members, HSF1 and HSF4b, whose transactivation capacities are repressed through the phosphorylation-dependent sumoylation. As the first recurrent sumoylation determinant beyond the consensus tetrapeptide, the PDSM provides a valuable tool in predicting new SUMO substrates.