title: A small peptide mimicking the key domain of MEPE/OF45 interacting with CHK1 protects human cells from radiation-induced killing.
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 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.
authors.affiliation: Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Xiangming
authors.initials: X
authors.lastname: Zhang
authors.forename: Peter
authors.initials: P
authors.lastname: Guida
authors.forename: Baocheng
authors.initials: B
authors.lastname: Hu
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects; D002461:Cell Line, Transformed; D000071877:Checkpoint Kinase 1; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010750:Phosphoproteins / Q000737:chemistry*; D011494:Protein Kinases / Q000378:metabolism*; D011839:Radiation, Ionizing; D051381:Rats
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C486579:MEPE protein, human; D010455:Peptides; D010750:Phosphoproteins; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605871:Chek1 protein, rat