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

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 fact...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2010-05, Vol.9 (10), p.1981-1985
Main Authors: Yu, Xiaoyan, Wang, Hongyan, Liu, Shuang, Zhang, Xiangming, Guida, Peter, Hu, Baocheng, Wang, Ya
Format: Article
Language:English
Subjects:
Animals
Binding
Biology
Bioscience
Blotting, Western
Calcium
Cancer
Cell
Cell Cycle - drug effects
Cell Cycle - radiation effects
Cell Line, Transformed
Checkpoint Kinase 1
Cycle
Extracellular Matrix Proteins - chemistry
G2 Phase - drug effects
G2 Phase - radiation effects
Glycoproteins - chemistry
Humans
Landes
Organogenesis
Peptides - chemistry
Peptides - metabolism
Peptides - pharmacology
Phosphoproteins - chemistry
Protein Kinases - metabolism
Proteins
Radiation, Ionizing
Rats
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Summary: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 induces 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.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.9.10.11651