Pallai Rajash, Bhaskar Aishwarya, Barnett-Bernodat Natalie, Gallo-Ebert Christina, Pusey Michelle, Nickels Joseph T, Rice Lyndi M
Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, Genesis Biotechnology Group, 1000 Waterview Drive, Hamilton, NJ, 08691, USA.
Tumour Biol. 2015 Aug;36(8):6383-90. doi: 10.1007/s13277-015-3326-1. Epub 2015 Apr 2.
Using yeast two-hybrid analysis, we identified several novel protein interactions for the oncoprotein Cancerous Inhibitor of PP2A (CIP2A) and confirmed a subset of these interactions in human cancer cell lines. Analysis of the interaction in prostate carcinoma cells between CIP2A and leucine-rich repeat-containing protein 59 (LRRC59) suggests that CIP2A is translocated into the nucleus at G2/M through its association with LRRC59. Recent work by others has demonstrated that nuclear CIP2A disrupts mitotic checkpoints, which promotes deregulation of the cell cycle and increases cancerous phenotypes. Thus, we provide a novel therapeutic mechanism for inhibiting CIP2A function in cancerous cells via targeting the CIP2A-LRRC59 interaction.
通过酵母双杂交分析，我们鉴定出了癌蛋白蛋白磷酸酶2A的癌性抑制剂（CIP2A）的几种新型蛋白质相互作用，并在人类癌细胞系中证实了其中一部分相互作用。对前列腺癌细胞中CIP2A与富含亮氨酸重复序列的蛋白59（LRRC59）之间相互作用的分析表明，CIP2A在G2/M期通过与LRRC59的结合而转运至细胞核。其他人最近的研究表明，细胞核中的CIP2A会破坏有丝分裂检查点，从而促进细胞周期失调并增加癌性表型。因此，我们提供了一种通过靶向CIP2A-LRRC59相互作用来抑制癌细胞中CIP2A功能的新型治疗机制。
