MIP-2A is a novel target of an anilinoquinazoline derivative for inhibition of tumour cell proliferation

MIP-2A 是苯胺喹唑啉衍生物抑制肿瘤细胞增殖的新靶点

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作者:Mayuko Tokunaga, Hirokazu Shiheido, Noriko Tabata, Yuko Sakuma-Yonemura, Hideaki Takashima, Kenichi Horisawa, Nobuhide Doi, Hiroshi Yanagawa

Abstract

We recently identified a novel anilinoquinazoline derivative, Q15, as a potent apoptosis inducer in a panel of human cancer cell lines and determined that Q15 targets hCAP-G2, a subunit of condensin II complex, leading to abnormal cell division. However, whether the defect in normal cell division directly results in cell death remains unclear. Here, we used an mRNA display method on a microfluidic chip to search for other Q15-binding proteins. We identified an additional Q15-binding protein, MIP-2A (MBP-1 interacting protein-2A), which has been reported to interact with MBP-1, a repressor of the c-Myc promoter. Our results indicate that Q15 inhibits the interaction between MIP-2A and MBP-1 as well as the expression of c-Myc protein, thereby inducing cell death. This study suggests that the simultaneous targeting of hCAP-G2 and MIP-2A is a promising strategy for the development of antitumor drugs as a treatment for intractable tumours.

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