Direct and distinguishable inhibitory roles for SUMO isoforms in the control of transcriptional synergy
Direct and distinguishable inhibitory roles for SUMO isoforms in the control of transcriptional synergy
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DOI：
10.1073/pnas.2136933100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Iñiguez-Lluhí, JA
中科院分区：
文献类型：
--
作者：
Holmstrom, S;Van Antwerp, ME;Iñiguez-Lluhí, JA
在DNA上的多个位点结合的因子之间的功能相互作用通常导致协同或超过加和的转录反应。我们先前定义了一类称为协同控制基序（SC基序）的肽序列，其通过选择性抑制由多个而非单个响应元件驱动的协同活性而在多个调节器中起作用。通过研究糖皮质激素受体的原型SC基序，我们表明，SC基序本身抑制转录顺式和反式，并与DNA的多次接触的要求，使他们选择性的复合反应元件。值得注意的是，SC基序是SUMO化的位点，修饰的程度与协同控制的程度密切相关。招募SUMO启动子独立或作为糖皮质激素受体的融合体足以概括SC基序的反式和顺式抑制作用，而不明显改变亚细胞定位。此外，我们发现SUMO的核心泛素折叠结构域足以抑制，并且独立于它们形成聚SUMO链的潜力，SUMO-2和SUMO-3是比SUMO-1更有效的抑制剂。
Functional interactions between factors bound at multiple sites on DNA often lead to a synergistic or more-than-additive transcriptional response. We previously defined a class of peptide sequences termed synergy control motifs (SC motifs) that function in multiple regulators by selectively inhibiting synergistic activity driven from multiple but not single response elements. By studying the prototypic SC motifs of the glucocorticoid receptor, we show that SC motifs inhibit transcription per se both in cis and in trans, and that a requirement for multiple contacts with DNA renders them selective for compound response elements. Notably, SC motifs are sites for SUMOylation, and the degree of modification correlates strongly with the extent of synergy control. Recruiting SUMO to the promoter either independently or as a fusion to the glucocorticoid receptor is sufficient to recapitulate the in trans and in cis inhibition by SC motifs without apparent changes in subcellular localization. Moreover, we find that the core ubiquitin fold domain of SUMO is sufficient for inhibition and that, independently of their potential for polySUMO chain formation, SUMO-2 and SUMO-3 are more effective inhibitors than SUMO-1.