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

页码：1403 / 1408

页数：6

共 32 条

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