Munirathinam Gnanasekar, Ramaswamy Kalyanasundaram
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA.
Biochem Res Int. 2012;2012:831940. doi: 10.1155/2012/831940. Epub 2012 Apr 11.
Translationally controlled tumor protein (TCTP) lacks nuclear bipartite localization signal sequence; yet TCTP is present abundantly in the nucleus. At present it is not known how TCTP gets transported to the nucleus. Sequence analyses showed that all TCTPs described to date have putative small ubiquitin-like modifier (SUMO) motifs. Since SUMO modification plays an important role in the nuclear transport of proteins, we evaluated whether SUMO motifs are important for transport of TCTP into the nucleus. We show that TCTP exists in sumoylated form in cytoplasm and nucleus of mammalian cells. Point mutation of lysine residue in the SUMO motif compromised the ability of TCTP to get sumoylated in vitro. When cells were transfected with FLAG-tagged mutated TCTP, nuclear transport of TCTP was inhibited confirming that sumoylation is critical for the nuclear transport of TCTP. Our previous studies demonstrated that TCTP can function as an antioxidant protein in the nucleus. When we mutated TCTP at the SUMO motif the antioxidant function of TCTP was compromised. Results presented in this study thus show that sumoylation plays an important role in the transport of TCTP into the nucleus where they function as antioxidant protein.
翻译调控肿瘤蛋白（TCTP）缺乏核双定位信号序列；然而TCTP在细胞核中大量存在。目前尚不清楚TCTP是如何转运到细胞核中的。序列分析表明，迄今为止描述的所有TCTP都有假定的小泛素样修饰物（SUMO）基序。由于SUMO修饰在蛋白质的核转运中起重要作用，我们评估了SUMO基序对于TCTP转运到细胞核是否重要。我们发现TCTP以SUMO化形式存在于哺乳动物细胞的细胞质和细胞核中。SUMO基序中赖氨酸残基的点突变损害了TCTP在体外进行SUMO化的能力。当用FLAG标记的突变TCTP转染细胞时，TCTP的核转运受到抑制，证实SUMO化对于TCTP的核转运至关重要。我们之前的研究表明，TCTP在细胞核中可作为抗氧化蛋白发挥作用。当我们在SUMO基序处突变TCTP时，TCTP的抗氧化功能受到损害。本研究结果表明，SUMO化在TCTP转运到细胞核中发挥重要作用，在细胞核中它们作为抗氧化蛋白发挥作用。
