title: Nuclear localization signal of ING4 plays a key role in its binding to p53.
abstract: 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.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Ke-Sheng
authors.initials: KS
authors.lastname: Wang
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Lu-Sheng
authors.initials: LS
authors.lastname: Xu
authors.forename: Qing-Wan
authors.initials: QW
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Dong-Zhi
authors.initials: DZ
authors.lastname: Wei
authors.forename: Ze-Guang
authors.initials: ZG
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002460:Cell Line; D019084:Fluorescent Antibody Technique, Indirect; D018398:Homeodomain Proteins; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D019913:Nuclear Localization Signals; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins