Regulation of DNA-dependent protein kinase activity in leukemic cells

被引:39
作者
Muller, C
Salles, B
机构
[1] CNRS,UPR 9062,INST PHARMACOL & BIOL STRUCT,F-31077 TOULOUSE,FRANCE
[2] CHU PURPAN,SERV HEMATOL,F-31300 TOULOUSE,FRANCE
关键词
DNA-PK; Ku autoantigen; CLL lymphocytes;
D O I
10.1038/sj.onc.1201402
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The DNA-dependent protein kinase (DNA-PK) complex is composed of a catalytic (DNA-PKcs), and a regulatory subunit (Ku70/Ku86 heterodimer), The expression and function of DNA-PK subunits was investigated in purified blood lymphocytes obtained from patients with chronic lymphocytic leukemia (CLL) either refractory to chemotherapy or untreated, Variations in DNA-PK activity were found amongst CLL samples by comparison to human cell lines, It was noticeable that the low DNA-PK activity was associated with samples from untreated patients that exhibited a sensitivity phenotype, determined in vitro, to the radiomimetic agent neocarcinostatin by comparison to samples from refractory patients, The regulation in DNA-PK activity was associated with Ku heterodimer expression while DNA-PKcs was unaffected, Moreover, the presence of an altered form of the Ku86 subunit was identified in samples with low DNA-PK activity, These results suggest a regulation process of the DNA-PK activity in fresh human cells.
引用
收藏
页码:2343 / 2348
页数:6
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