%0 Journal Article
%T Tip60 Tumor Suppressor Requires Its NLS Motif to Interact with Importin <i>¦Á</i>
%A Eun Jeoung Lee
%A Sung Hwa Shin
%A Sang Sun Kang
%J CellBio
%P 1-16
%@ 2325-7792
%D 2019
%I Scientific Research Publishing
%R 10.4236/cellbio.2019.81001
%X Tip60 is a specific member of MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of nuclear histone acetyltransferases (HAT). It is essential for cellular survival, differentiation, and metabolism. A putative canonical NLS motif between the chromo domain and the zinc finger of Tip60 was identified. Here we show evidence that Tip60 is associated with importin ¦Á as its substrate and transported from cytoplasm to the nucleus. Pull down assay revealed that Tip60 was physically associated with importin ¦Á both in vivo and in vitro. Confocal microscopic observation showed that Tip60 and importin ¦Á were co-localized with each other. The localization of Tip60 to the nuclear and its interaction with importin ¦Á was disrupted when its putative NLS motif for binding to importin ¦Á was mutated (219RKRK222 → 219AAAA222). However, attachment of this putative NLS motif to a cytoplasmic protein (YAP 1-210 fragment) promoted its nuclear localization. Based on transient transfection, Tip60 NLS motif mutant showed a substantial reduction in self-acetylation, HAT activity, and apoptotic ability whereas wild type Tip60 did not show such reduction. Taken together, our results demonstrate that importin ¦Á transports Tip60 from the cytoplasm to the nucleus through binding to the putative NLS motif of Tip60 for its tumor suppressing function.
%K Tip60
%K Importin ¦Á
%K Nuclear Localization Sequence
%K Protein-Protein Interaction
%K HAT Activity
%K Cell Survival
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=91893