Translationally controlled tumor protein (TCTP) has both extra- and intracellular functions. Our group recently reported that TCTP interacts with Na,K-ATPase and suppresses its activity. Our studies led to the identification of sorting nexin 6 (SNX6) which binds with TCTP as a potential negative regulator of TCTP. SNX6 does not interact directly with any cytoplasmic domains of Na,K-ATPase. However, when overexpressed, it restores the Na,K-ATPase activity suppressed by TCTP. This was confirmed by measurements of purified plasma membrane Na,K-ATPase activity after incubation with recombinant TCTP and SNX6. SNX6 alone has no effect on Na,K-ATPase activity, but activates Na,K-ATPase via inhibition of TCTP. Inhibition of endogenous TCTP by the overexpression of SNX6 or knockdown of TCTP expression by siTCTP increased Na,K-ATPase activity above the basal level. The interaction between SNX6 and TCTP thus appears to regulate Na,K-ATPase activity.
Bibliographical noteFunding Information:
We thank Jaehoon Jung for advice on 86 Rb + uptake and in vitro Na,K-ATPase activity assays. This work was supported by Korea Research Foundation Grant funded by Korea Government (MOEHRD, Basic Research Promotion Fund), Korean Health 21 R&D Project by Ministry of Health and Welfare (A050402), Seoul R&BD Program, and the Korea Science and Engineering Foundation through CCSR at Ewha Womans University. T. Yoon was supported by the Brain Korea 21 Project Fellowship.
- Sorting nexin 6
- Translationally controlled tumor protein