55K isoform of CDK9 associates with Ku70 and is involved in DNA repair
Abstract
Positive elongation factor b (P-TEFb) is a cellular protein kinase that is required for RNA polymerase II (RNAP II) transcriptional elongation of protein coding genes. P-TEFb is a set of different molecular complexes, each containing CDK9 as the catalytic subunit. There are two isoforms of the CDK9 protein - the major 42 KDa CDK9 isoform and the minor 55KDa isoform that is translated from an in-frame mRNA that arises from an upstream transcriptional start site. We found that shRNA depletion of the 55K CDK9 protein in HeLa cells induces apoptosis and double-strand DNA breaks (DSBs). The levels of apoptosis and DSBs induced by the depletion were reduced by expression of a 55K CDK9 protein variant resistant to the shRNA, indicating that these phenotypes are the consequence of depletion of the 55K protein and not off-target effects. We also found that the 55K CDK9 protein, but not the 42K CDK9 protein, specifically associates with Ku70, a protein involved in DSB repair. Our findings suggest that the 55K CDK9 protein may function in repair of DNA through an association with Ku70.
- Authors:
-
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030 (United States)
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States)
- Publication Date:
- OSTI Identifier:
- 22202662
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 397; Journal Issue: 2; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; APOPTOSIS; DNA; DNA REPAIR; GENES; HELA CELLS; MESSENGER-RNA; PHENOTYPE; POTASSIUM 55; PROTEINS
Citation Formats
Liu, Hongbing, Herrmann, Christine H., Chiang, Karen, Sung, Tzu-Ling, Moon, Sung-Hwan, Donehower, Lawrence A., Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, and Rice, Andrew P., E-mail: arice@bcm.edu. 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. United States: N. p., 2010.
Web. doi:10.1016/J.BBRC.2010.05.092.
Liu, Hongbing, Herrmann, Christine H., Chiang, Karen, Sung, Tzu-Ling, Moon, Sung-Hwan, Donehower, Lawrence A., Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, & Rice, Andrew P., E-mail: arice@bcm.edu. 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. United States. https://doi.org/10.1016/J.BBRC.2010.05.092
Liu, Hongbing, Herrmann, Christine H., Chiang, Karen, Sung, Tzu-Ling, Moon, Sung-Hwan, Donehower, Lawrence A., Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, and Rice, Andrew P., E-mail: arice@bcm.edu. 2010.
"55K isoform of CDK9 associates with Ku70 and is involved in DNA repair". United States. https://doi.org/10.1016/J.BBRC.2010.05.092.
@article{osti_22202662,
title = {55K isoform of CDK9 associates with Ku70 and is involved in DNA repair},
author = {Liu, Hongbing and Herrmann, Christine H. and Chiang, Karen and Sung, Tzu-Ling and Moon, Sung-Hwan and Donehower, Lawrence A. and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 and Rice, Andrew P., E-mail: arice@bcm.edu},
abstractNote = {Positive elongation factor b (P-TEFb) is a cellular protein kinase that is required for RNA polymerase II (RNAP II) transcriptional elongation of protein coding genes. P-TEFb is a set of different molecular complexes, each containing CDK9 as the catalytic subunit. There are two isoforms of the CDK9 protein - the major 42 KDa CDK9 isoform and the minor 55KDa isoform that is translated from an in-frame mRNA that arises from an upstream transcriptional start site. We found that shRNA depletion of the 55K CDK9 protein in HeLa cells induces apoptosis and double-strand DNA breaks (DSBs). The levels of apoptosis and DSBs induced by the depletion were reduced by expression of a 55K CDK9 protein variant resistant to the shRNA, indicating that these phenotypes are the consequence of depletion of the 55K protein and not off-target effects. We also found that the 55K CDK9 protein, but not the 42K CDK9 protein, specifically associates with Ku70, a protein involved in DSB repair. Our findings suggest that the 55K CDK9 protein may function in repair of DNA through an association with Ku70.},
doi = {10.1016/J.BBRC.2010.05.092},
url = {https://www.osti.gov/biblio/22202662},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 397,
place = {United States},
year = {Fri Jun 25 00:00:00 EDT 2010},
month = {Fri Jun 25 00:00:00 EDT 2010}
}