Facilitation of SUMO (Small Ubiquitin-like Modifier) Modification at Tau 340-Lys Residue (a Microtubule-associated Protein) through Phosphorylation at 214-Ser Residue

• Published in: Integrative biosciences 2007, Vol.11 (1), p.39-50
• Main Authors: Lee, Eun-Jeoung, Hyun, Sung-Hee, Chun, Jae-Sun, Ahn, Hye-Rim, Kang, Sang-Sun
• Format: Article
• Language: Korean
• ISSN: 1738-6357; 1738-7078

Tau plays a role in numerous neuronal processes, such as vesicle transport, microtubule-plasma membrane interaction and intracellular localization of proteins. SUMO (Small Ubiquitin-like Modifier) modification (SUMOylation) appears to regulate diverse cellular processes including nuclear transport, signal transduction, apoptosis, autophagy, cell cycle control, ubiquitin-dependent degradation, as well as gene transcription. We noticed that putative SUMOylation site is localized at $^{340}K$ of $Tau(^{339}VKSE^{342})$ with the consensus sequence information (${\Phi}KxE$ ; where ${\Phi}$ represents L, I, V or F and x is any amino acid). In this report, we demonstrated that $^{340}K$ of Tau is the SUMOylation site and that a point mutant of Tau S214E (an analog of the phospho $^{214}S$ Tau) promotes its SUMOylation at $^{340}K$ and its nuclear or nuclear vicinity localization, by co-immunoprecipitation and confocal microscopy analysis. Further, we demonstrate that the Tau S214E (neither Tau S214A nor Tau K340R) mutant increases its protein stability. However, the SUMOylation at $^{340}K$ of Tau did not influence cell survival, as determined by FACS analysis. Therefore, our results suggested that the phosphorylation of Tau on $^{214}S$ residue promotes its SUMOylation on $^{340}K$ residue and nuclear vicinity localization, and increases its stability, without influencing cell survival.