RGD Reference Report - The radioresistance to killing of A1-5 cells derives from activation of the Chk1 pathway. - Rat Genome Database

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The radioresistance to killing of A1-5 cells derives from activation of the Chk1 pathway.

Authors: Hu, B  Zhou, XY  Wang, X  Zeng, ZC  Iliakis, G  Wang, Y 
Citation: Hu B, etal., J Biol Chem. 2001 May 25;276(21):17693-8. Epub 2001 Mar 7.
RGD ID: 2316109
Pubmed: PMID:11278490   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M009340200   (Journal Full-text)

Checkpoints respond to DNA damage by arresting the cell cycle to provide time for facilitating repair. In mammalian cells, the G(2) checkpoint prevents the Cdc25C phosphatase from removing inhibitory phosphate groups from the mitosis-promoting kinase Cdc2. Both Chk1 and Chk2, the checkpoint kinases, can phosphorylate Cdc25C and inactivate its in vitro phosphatase activity. Therefore, both Chk1 and Chk2 are thought to regulate the activation of the G(2) checkpoint. Here we report that A1-5, a transformed rat embryo fibroblast cell line, shows much more radioresistance associated with a much stronger G(2) arrest response when compared with its counterpart, B4, although A1-5 and B4 cells have a similar capacity for nonhomologous end-joining DNA repair. These phenotypes of A1-5 cells are accompanied by a higher Chk1 expression and a higher phosphorylation of Cdc2. On the other hand, Chk2 expression increases slightly following radiation; however, it has no difference between A1-5 and B4 cells. Caffeine or UCN-01 abolishes the extreme radioresistance with the strong G(2) arrest and at the same time reduces the phosphorylation of Cdc2 in A1-5 cells. In addition, Chk1 but not Chk2 antisense oligonucleotide sensitizes A1-5 cells to radiation-induced killing and reduces the G(2) arrest of the cells. Taken together these results suggest that the Chk1/Cdc25C/Cdc2 pathway is the major player for the radioresistance with G(2) arrest in A1-5 cells.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Chek1Ratprotein kinase activity  IDA  RGD 
Chek2Ratprotein kinase activity  IDA  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CHEK1HumanG2/M DNA damage checkpoint pathway  ISOChek1 (Rattus norvegicus) RGD 
Chek1MouseG2/M DNA damage checkpoint pathway  ISOChek1 (Rattus norvegicus) RGD 
Chek1RatG2/M DNA damage checkpoint pathway  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Chek1  (checkpoint kinase 1)
Chek2  (checkpoint kinase 2)

Genes (Mus musculus)
Chek1  (checkpoint kinase 1)

Genes (Homo sapiens)
CHEK1  (checkpoint kinase 1)


Additional Information