Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
Biochem J. 2010 May 13;428(2):247-54. doi: 10.1042/BJ20091948.
The modification of proteins with SUMO (small ubiquitin-related modifier) plays an important role in determining their functional properties. Importantly though, SUMOylation is a highly dynamic process enabling transient responses to be elicited. This dynamism is controlled by two competing conjugating and deconjugating activities. The latter activity is mediated by the SENP [SUMO1/sentrin/SMT3 (suppressor of mif two 3 homologue 1)-specific peptidase] family of SUMO-specific proteases. The transcription factor Elk-1 [ETS (E twenty-six)-like 1] undergoes rapid de-SUMOylation following cellular stimulation with growth factors, and this contributes to its conversion from a SUMO-dependent repressor into a potent transcriptional activator. In the present study we demonstrate an important role for SENP1 in the de-SUMOylation of Elk-1, and therefore an integral role in determining the Elk-1-dependent transcriptional programme. Among the SENPs, Elk-1 preferentially forms a complex with SENP1. This preferential binding is reflected by the higher efficiency of SENP1 in promoting Elk-1 transactivation. Moreover, depletion of SENP1 causes a reciprocal effect and reduces the transactivation properties of Elk-1. Partial redundancy of function with SENP2 is revealed by combinatorial knockdown studies. Importantly, depletion of SENP1 also reduces the activation of the Elk-1 target gene c-FOS. Taken together, these results therefore reveal an important role for SENP1 in the regulation of Elk-1-mediated gene expression in response to mitogenic signalling cues.
蛋白质的 SUMO（小泛素相关修饰物）修饰在决定其功能特性方面起着重要作用。然而，重要的是，SUMOylation 是一个高度动态的过程，能够引发瞬时反应。这种动态性由两种竞争性的连接和去连接活性控制。后者的活性由 SENP（SUMO1/sentrin/SMT3（抑制 mif 两个 3 同源物 1）特异性肽酶）家族的 SUMO 特异性蛋白酶介导。转录因子 Elk-1（ETS（E 二十六个）样 1）在细胞受到生长因子刺激后迅速去 SUMOylation，这有助于其从 SUMO 依赖性抑制剂转化为有效的转录激活剂。在本研究中，我们证明了 SENP1 在 Elk-1 的去 SUMOylation 中起重要作用，因此在决定 Elk-1 依赖性转录程序中起重要作用。在 SENPs 中，Elk-1 优先与 SENP1 形成复合物。这种优先结合反映在 SENP1 促进 Elk-1 转录激活的效率更高。此外，SENP1 的耗竭会产生相反的效果，并降低 Elk-1 的转录激活特性。通过组合敲低研究揭示了 SENP2 的部分功能冗余。重要的是，SENP1 的耗竭也会降低 Elk-1 靶基因 c-FOS 的激活。总之，这些结果揭示了 SENP1 在调节 Elk-1 介导的基因表达方面的重要作用，以响应有丝分裂信号线索。
