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

• Type of Material: Article
• Authors: Xiaoyan Yu, Emory University; Hongyan Wang, Emory University; Shuang Liu, Emory University; Xiangming Zhang, Emory University; Peter Guida, Brookhaven National Laboratory; Baocheng Hu, Emory University; Ya Wang, Emory University
• Language: English
• Date: 2010-05-15
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 Landes Bioscience.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.4161/cc.9.10.11651
• Title of Journal or Parent Work: Cell Cycle
• ISSN: 1538-4101
• Volume: 9
• Issue: 10
• Start Page: 1981
• End Page: 1985
• Grant/Funding Information: This work is supported by grants from the National Basic Research Program of China (2005CB522506 and 2007CB914604 to B.H.); the National Natural Science Foundation of China (30770651, 30670616 and 30370441 to B.H.); and the grants from the National Institutes of Health; and from National Aeronautics and Space Administration USA (GM080771 and NNX07AT40G to Y.W.).
• Keywords: S-PHASE CELLS; MEPE/OF45; GENE; CHECKPOINT RESPONSE; ionizing radiation; Cell Biology; CHK1; Science & Technology; Life Sciences & Biomedicine; ATR; BONE; IONIZING-RADIATION; HOMOLOGOUS RECOMBINATION REPAIR; ATR/CHK1 PATHWAY; RADIOSENSITIVITY; ENERGY-TRANSFER RADIATION
• Research Categories: Biology, Cell; Physics, Radiation

Abstract

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 CH3(CH2)8CO. After the 18 aa peptide entered the human cells, it interacted with CHK1, increased the CHK1 level and induced a stronger G2 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.