Can your protein be sumoylated? A quick summary and important tips to study SUMO-modified proteins

A diverse set of SUMO target proteins has been identified. Therefore, there is a growing interest in studying sumoylation and SUMO interactions in cells. When the sumoylation of a protein or a SUMO interaction is suspected, a standard co-immunoprecipitation analysis using anti-SUMO and anti-target protein antibody is usually performed as a first step. However, the identification of endogenous sumoylated proteins is challenging because of the activity of isopeptidases, and often only a small fraction of a target protein is sumoylated at a given time. Here, we briefly summarize several important steps to ensure a successful co-immunoprecipitation analysis to detect possible sumoylation.     

SUMO化修饰与DNA损伤修复

由于体内外因素的影响,DNA损伤是生物生命周期中的常见现象,如果得不到及时的修复,DNA损伤的积累将导致基因组的不稳定及染色质的异常,并可能导致肿瘤的发生发展。SUMO化修饰是体内一个重要的蛋白质翻译后修饰,越来越多的研究发现SUMO化修饰与多个参与DNA损伤反应、维持基因组稳定的蛋白质相关,有可能参与肿瘤的发生。本文将阐述SUMO化修饰与DNA损伤修复的关系。     

炎症反应中的蛋白质翻译后修饰

炎症相关的信号转导蛋白、转录因子、炎性介质、组蛋白等可在炎症发生发展过程中发生磷酸化、乙酰化、泛素化、苏素化、甲基化等一系列翻译后修饰。这些化学修饰可高效调节相关蛋白质的功能活性及基因表达水平,不同化学修饰之间还可相互作用,共同影响炎症的发生、发展与转归;而异常的翻译后修饰与炎症相关性疾病关系密切。     

Ubiquitin-specific Protease 11 (USP11) Deubiquitinates Hybrid Small Ubiquitin-like Modifier (SUMO)-Ubiquitin Chains to Counteract RING Finger Protein 4 (RNF4)

Ring finger protein 4 (RNF4) is a SUMO-targeted ubiquitin E3 ligase with a pivotal function in the DNA damage response (DDR). SUMO interaction motifs (SIMs) in the N-terminal part of RNF4 tightly bind to SUMO polymers, and RNF4 can ubiquitinate these polymers in vitro. Using a proteomic approach, we identified the deubiquitinating enzyme ubiquitin-specific protease 11 (USP11), a known DDR-component, as a functional interactor of RNF4. USP11 can deubiquitinate hybrid SUMO-ubiquitin chains to counteract RNF4. SUMO-enriched nuclear bodies are stabilized by USP11, which functions downstream of RNF4 as a counterbalancing factor. In response to DNA damage induced by methyl methanesulfonate, USP11 could counteract RNF4 to inhibit the dissolution of nuclear bodies. Thus, we provide novel insight into cross-talk between ubiquitin and SUMO and uncover USP11 and RNF4 as a balanced SUMO-targeted ubiquitin ligase/protease pair with a role in the DDR.     

Protein interactions on telomeric retrotransposons in Drosophila

Telomere length in Drosophila is maintained by targeted transposition of three non-LTR retrotransposons: HeT-A, TART and TAHRE (HTT), but understanding the regulation of this process is hindered by our poor knowledge of HTT associated proteins. We have identified new protein components of the HTT array: Chromator (Chro), the TRF2/DREF complex and the sumoylation machinery. Chro was localized on telomeric HTT arrays by immunostaining, where it may interact with Prod directly, as indicated by yeast two-hybrid interaction, co-IP, and colocalization on polytene chromosomes. The TRF2/DREF complex may promote the open structure of HTT chromatin. The protein interactions controlling HTT chromatin structure and telomere length may be modulated by sumoylation.