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Catalytic subunit of DNA-dependent protein kinase: Impact on lymphocyte development and tumorigenesis

被引：151
作者：
Kurimasa, A
Ouyang, H
Dong, LJ
Wang, S
Li, XL
Cordon-Cardo, C
Chen, DJ
Li, GC
机构：
[1] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Phys Med, New York, NY 10021 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA
[4] Univ Calif Los Alamos Natl Lab, Div Life Sci, Los Alamos, NM 87545 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1999年 / 96卷 / 04期
关键词：
D O I：
10.1073/pnas.96.4.1403
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The DNA-dependent protein kinase (DNA-PK) consists of a heterodimer DNA-binding complex, Ku70 and Ku80, and a large catalytic subunit, DNA-PKcs, To examine the role of DNA-PKcs in lymphocyte development, radiation sensitivity, and tumorigenesis, we disrupted the mouse DNA-PKcs by homologous recombination. DNA-PKcs-null mice exhibit neither growth retardation nor a high frequency of T cell lymphoma development, but show severe immunodeficiency and radiation hypersensitivity. In contrast to the Ku70-/- and Ku80-/- phenotype, DNA-PKcs-null mice are blocked for V(D)J coding but not for signal-end joint formation. Furthermore, inactivation of DNA-PKcs leads to hyperplasia and dysplasia of the intestinal mucosa and production of aberrant crypt foci, suggesting a novel role of DNA-PKcs in tumor suppression.
引用
收藏
页码：1403 / 1408
页数：6
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