NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression
NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression
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DOI：
10.1073/pnas.0601066103
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发表时间：
2006-04-04
影响因子：
11.1
通讯作者：
Gill, G
中科院分区：
文献类型：
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作者：
Rosendorff, A;Sakakibara, S;Gill, G
转录因子的小泛素样修饰物（SUMO）修饰通常与阻遏有关。SUMO-1和-2保守残基的反向遗传分析强调了双电荷反转在消除SLIMO-2 K33、K35和K42在阻遏中的关键作用中的重要性。GST-SUMO-2-亲和层析，然后进行液相层析（LC）-MS分析，鉴定了似乎优先结合WT SUMO-2而不是SUMO-2 K33 E和K35 E的蛋白质。LSD 11、NXP-2、KIAA 0809（ARIP 4）、SAE 2、RanGAP 1、PELP 1和SETDB 1与SUMO-2结合，而不与SUMO-2 K33 E、K42 E或K35 E和K42 E结合。虽然LSD 1是一种组蛋白赖氨酸脱甲基酶，组蛋白H3 K4在SUMO-2抑制的启动子处被clemethylated，但无论是显性负性LSD 1的过表达还是用RNA干扰的LSD 1耗尽都不会影响SUMO-2介导的抑制，这表明在这种情况下，LSD 1对于抑制不是必需的。当通过与Ga 14融合而与启动子连接时，NXP-2抑制转录，这与NXP-2在SUMO介导的抑制中的作用一致。在这项研究中发现的SUMO-2相关蛋白可能有助于SUMO依赖的转录或其他过程的调节。
Small ubiquitin-like modifier (SUMO) modification of transcription factors is generally associated with repression. Reverse genetic analysis of SUMO-1, and -2 conserved residues emphasized the importance of dual charge reversals in abrogating the critical role of SLIMO-2 K33, K35, and K42 in repression. GST-SUMO-2-affinity chromatography followed by liquid chromatography (LC)-MS analysis identified proteins that appeared to bind preferentially to WT SUMO-2 versus SUMO-2 K33E and K35E. LSD11, NXP-2, KIAA0809 (ARIP4), SAE2, RanGAP1, PELP1, and SETDB1 bound to SUMO-2 and not to SUMO-2 K33E, K42E, or K35E and K42E. Although LSD1 is a histone lysine demethylase, and histone H3K4 was clemethylated at a SUMO-2-repressed promoter, neither overexpression of a dominant-negative LSD1 nor LSD1 depletion with RNA interference affected SUMO-2-mediated repression, indicating that LSD1 is not essential for repression, in this context. When tethered to a promoter by fusion to Ga14, NXP-2 repressed transcription, consistent with a role for NXP-2 in SUMO-mediated repression. SUMO-2-associated proteins identified in this study may contribute to SUMO-dependent regulation of transcription or other processes.