Sumoylation is important for the nuclear transport and antioxidant function of the translationally controlled tumor protein

Abstract

Translationally controlled tumor protein (TCTP) is one of the most abundantly expressed proteins in the cell. Several functions have been suggested for TCTP family of proteins ranging from calcium binding to histamine release. Nevertheless, its physiological function within the cell is still a mystery. TCTP is present abundantly in the nucleus despite the absence of a nuclear localization signal. Sequence analysis showed that all TCTPs described to date has small ubiquitin‐like modifier (SUMO) motifs. Since SUMO modification plays an important role in the nuclear transport of proteins, we evaluated whether sumoylation is important for the nuclear transport of TCTP. Initial studies confirmed that sumoylated form of TCTP is present in the cytoplasm and nucleus of mammalian cells. Point mutation studies confirmed that sumoylation is important for the transport of TCTP into the nucleus. Previous studies also showed that the expression of TCTP is increased several fold during oxidative stress. To test whether nuclear TCTP has any role in protecting DNA from oxidative stress, we first reduced TCTP with thioredoxin and used this reduced TCTP in our assays. These studies showed that TCTP can protect DNA from oxidative damage. Targeted point mutation studies showed that certain residues in TCTP are critical for this antioxidant function. Knocking down of the TCTP with SiRNA or mutating the TCTP at the SUMO motif failed to confer the anti‐oxidant protection. These studies thus demonstrate that TCTP has significant antioxidant property within the nucleus. This study is supported by NIH grant AI064745 to Dr. K. Ramaswamy