Nuclear localization signal of ING4 plays a key role in its binding to p53

• Published in: Biochemical and biophysical research communications Vol. 331; no. 4; pp. 1032 - 1038
• Main Authors: Zhang, Xin, Wang, Ke-Sheng, Wang, Zhi-Qin, Xu, Lu-Sheng, Wang, Qing-Wan, Chen, Fei, Wei, Dong-Zhi, Han, Ze-Guang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.06.2005
• Subjects: Amino Acid Sequence; Cell Cycle Proteins; Cell Line; Fluorescent Antibody Technique, Indirect; Homeodomain Proteins; Humans; ING4; Molecular Sequence Data; Nuclear localization signal; Nuclear Localization Signals; p21; p53; Protein Binding; Protein–protein interaction; Sequence Homology, Amino Acid; Subcellular localization; Transcriptional activity; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - metabolism; ING4; Subcellular localization; Nuclear localization signal; Transcriptional activity; Protein–protein interaction; p21; p53
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.04.023

ING4, a novel member of ING family, is recently reported to interact with tumor suppressor p53 and negatively regulate the cell growth with significant G2/M arrest of cell cycle in HepG2 cells through upregulation of p53-inducible gene p21. However, which region of ING4 could have contributed to the binding to p53 remains largely unclear. Herein, the GST-pulldown experiments revealed that the middle region of ING4, a potential bipartite nuclear localization signal (NLS), could be involved in the binding to p53. Furthermore, the interaction of ING4 to p53 was abrogated in vitro and in vivo when certain mutations or the entire deletion of the NLS domain occurred. More interestingly, the mutations of the NLS domain could alter the ING4 nuclear localization, disrupt the interaction of ING4 with p53, and even, deregulate the p53-inducible gene p21 in MCF-7 cells. All data indicated that the NLS domain of ING4 is essential for the binding of ING4 to p53 and the function of ING4 associated with p53.