Abstract
Tip60 exerts diverse biological functions through mechanisms that are either dependent or independent on its intrinsic histone acetyltransferase activity. In the present study, we identified Nmi (N-Myc and STATs Interactor) as a novel binding partner for Tip60 by a yeast two-hybrid screen. The association of Tip60 with Nmi was further confirmed by coimmunoprecipitation in mammalian cells. The zinc finger domain of Tip60 interacts with the NID repeats of Nmi, a region essential for the cytoplamic localization and homo- and heterodimerization of Nmi. We further showed that Nmi is an unstable protein and is targeted for proteasome-mediated degradation. The stability of Nmi can be enhanced by its association with Tip60, a process that is dependent on histone acetyltransferase activity of Tip60. The stabilization of Nmi by Tip60 is in part mediated by the translocation of Tip60 into cytoplasm to form distinct large cytoplasmic speckles. Our finding that Tip60 stabilizes Nmi through the formation of distinct cytoplasmic speckles provides a new mechanism to modulate Nmi-mediated functions.
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Acknowledgments
We thank Dr. Louie Naumovski for providing pCEP4 Flag-Nmi, pEGFP-Nmi and various deletion mutants of pCEP4 Flag-Nmi. This study was supported by NIH grants RO1DK50570 and RO1HL76919 (to Y-C.Y.).
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Zhang, K., Zheng, G. & Yang, YC. Stability of Nmi protein is controlled by its association with Tip60. Mol Cell Biochem 303, 1–8 (2007). https://doi.org/10.1007/s11010-007-9449-y
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DOI: https://doi.org/10.1007/s11010-007-9449-y