CellBio  Vol.8 No.1 , March 2019
Tip60 Tumor Suppressor Requires Its NLS Motif to Interact with Importin α
Abstract: 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 α as its substrate and transported from cytoplasm to the nucleus. Pull down assay revealed that Tip60 was physically associated with importin α both in vivo and in vitro. Confocal microscopic observation showed that Tip60 and importin α were co-localized with each other. The localization of Tip60 to the nuclear and its interaction with importin α was disrupted when its putative NLS motif for binding to importin α was mutated (219RKRK222 &#8594 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 α transports Tip60 from the cytoplasm to the nucleus through binding to the putative NLS motif of Tip60 for its tumor suppressing function.
Cite this paper: Lee, E. , Shin, S. and Kang, S. (2019) Tip60 Tumor Suppressor Requires Its NLS Motif to Interact with Importin α. CellBio, 8, 1-16. doi: 10.4236/cellbio.2019.81001.

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