A small peptide mimicking the key domain of MEPE/OF45 interacting with CHK1 protects human cells from radiation-induced killing

作者：Yu, Xiaoyan; Wang, Hongyan; Liu, Shuang; Zhang, Xiangming; Guida, Peter; Hu, Baocheng; Wang, Ya^*

来源：Cell Cycle, 2010, 9(10): 1981-1985.

DOI：10.4161/cc.9.10.11651

• MEPE/OF45
• CHK1
• ionizing radiation

Checkpoint activation benefits DNA homologous recombination repair and; therefore, protects cells from ionizing radiation (IR)-induced killing. CHK1 is one of the most important checkpoint regulators in mammalian cells. We recently reported that matrix extracellular phosphoglycoprotein/osteoblast factor 45 (MEPE/OF45) stabilizes CHK1 through interacting with CHK1, thus protecting cells from IR-induced killing. The purpose of this study is to investigate whether a small peptide that mimics the key domain of MEPE/OF45 could interact with CHK1 and protect cells from IR-induced killing. We showed here that the synthesized peptide with 18 amino acids (aa) could enter human transformed lymphoblasts when it is linked to fatty acid CH 3 (CH 2) 8 CO. After the 18 aa peptide entered the human cells, it interacted with CHK1, increased the CHK1 level and induced a stronger G 2 arrest in the cells following IR. More importantly, the 18 aa peptide could protect the cells from IR-induced killing. Our data indicate that the 18 aa peptide, similar to MEPE/OF45, reduces CHK1 degradation and protects cells from IR-induced killing. We believe that these results provide useful information for drug development in two directions: protect cells from IR-induced damage and sensitize cells to radiation therapy.

• 出版日期2010-5-15
• 单位吉林大学; 佳木斯大学