TY - JOUR
T1 - MIP-2A Is a Novel Target of an Anilinoquinazoline Derivative for Inhibition of Tumour Cell Proliferation
AU - Tokunaga, Mayuko
AU - Shiheido, Hirokazu
AU - Tabata, Noriko
AU - Sakuma-Yonemura, Yuko
AU - Takashima, Hideaki
AU - Horisawa, Kenichi
AU - Doi, Nobuhide
AU - Yanagawa, Hiroshi
PY - 2013/9/30
Y1 - 2013/9/30
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0076774
DO - 10.1371/journal.pone.0076774
M3 - Article
C2 - 24098805
AN - SCOPUS:84884784314
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 9
M1 - e76774
ER -