DOI: 10.1073/pnas.96.4.1403. Catalytic subunit of DNA-dependent protein kinase: Impact on lymphocyte development and tumorigenesis

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

10.1073/pnas.96.4.1403

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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.

Bibliography

Kurimasa, A., Ouyang, H., Dong, L., Wang, S., Li, X., Cordon-Cardo, C., Chen, D. J., & Li, G. C. (1999). Catalytic subunit of DNA-dependent protein kinase: Impact on lymphocyte development and tumorigenesis. Proceedings of the National Academy of Sciences, 96(4), 1403â1408.

Authors 8

Akihiro Kurimasa (first)
Honghai Ouyang (additional)
Li-jin Dong (additional)
Sa Wang (additional)
Xiaoling Li (additional)
Carlos Cordon-Cardo (additional)
David J. Chen (additional)
Gloria C. Li (additional)

References 32 Referenced 144

10.1073/pnas.92.8.3171
10.1016/0092-8674(95)90360-7
10.1126/science.7855601
10.1074/jbc.271.15.8936
10.1073/pnas.91.15.6904
10.1093/emboj/16.16.5098
10.1073/pnas.95.2.525
10.1128/MCB.16.10.5507
10.1073/pnas.94.6.2438
10.1073/pnas.93.19.10285
10.1038/ng1297-483
R P Custer, G C Bosma, M J Bosma Am J Pathol 120, 464–477 (1985). / Am J Pathol by Custer R P (1985)
10.1038/382551a0
10.1016/S1097-2765(00)80108-2
10.1074/jbc.272.15.10227
10.1084/jem.186.6.921
10.1128/mcb.10.12.6460-6471.1990
10.1016/S0092-8674(00)81079-X
10.1016/S0092-8674(00)80111-7
10.1016/S1074-7613(00)80619-6
10.1016/S1074-7613(00)80618-4
10.1016/S1074-7613(00)80386-6
C J A Moen, M A van der Valk, R P Bird, A M Augustinus, P Demant Cancer Res 56, 2382–2386 (1996). / Cancer Res by Moen C J A (1996)
L Roncussi, M Pedroni, R Fante, C Di Gregorio, M Ponz de Leon Cancer Res 53, 3726–3729 (1993). / Cancer Res by Roncussi L (1993)
10.1016/0304-3835(95)03788-X
10.1016/0168-9525(93)90209-Z
10.1016/S0092-8674(00)81333-1
10.1093/oxfordjournals.jbchem.a022143
10.1074/jbc.270.3.1449
10.1073/pnas.91.18.8343
10.1016/0968-0004(93)90144-C
10.1007/s003359900861

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:53 p.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 3:07 p.m.)
Issued	26 years, 6 months ago (Feb. 16, 1999)
Published	26 years, 6 months ago (Feb. 16, 1999)
Published Online	26 years, 6 months ago (Feb. 16, 1999)
Published Print	26 years, 6 months ago (Feb. 16, 1999)

Funders 0

None

BibTeX

@article{Kurimasa_1999, title={Catalytic subunit of DNA-dependent protein kinase: Impact on lymphocyte development and tumorigenesis}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.4.1403}, DOI={10.1073/pnas.96.4.1403}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kurimasa, Akihiro and Ouyang, Honghai and Dong, Li-jin and Wang, Sa and Li, Xiaoling and Cordon-Cardo, Carlos and Chen, David J. and Li, Gloria C.}, year={1999}, month=feb, pages={1403–1408} }

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