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Inactivation of DNA-Dependent Protein Kinase by Protein Kinase Cδ: Implications for Apoptosis
Open accessAbstract
Protein kinase Cdelta (PKCdelta) is proteolytically cleaved and activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. A role for PKCdelta in apoptosis is supported by the finding that overexpression of the catalytic fragment of PKCdelta (PKCdelta CF) in cells is associated with the appearance of certain characteristics of apoptosis. However, the functional relationship between PKCdelta cleavage and induction of apoptosis is unknown. The present studies demonstrate that PKCdelta associates constitutively with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The results show that PKCdelta CF phosphorylates DNA-PKcs in vitro. Interaction of DNA-PKcs with PKCdelta CF inhibits the function of DNA-PKcs to form complexes with DNA and to phosphorylate its downstream target, p53. The results also demonstrate that cells deficient in DNA-PK are resistant to apoptosis induced by overexpressing PKCdelta CF. These findings support the hypothesis that functional interactions between PKCdelta and DNA-PK contribute to DNA damage-induced apoptosis.
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Cited by
Protein kinase C and other diacylglycerol effectors in cancer
Griner, E. M., & Kazanietz, M. G. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2110 · Cited by 978
Structural Basis of Protein Kinase C Isoform Function
Steinberg, S. F. (2008) · Physiological Reviews · doi:10.1152/physrev.00034.2007 · Cited by 872
Atypical protein kinase C stimulates nucleotide excision repair activity
Louat, T., Canitrot, Y., Jousseaume, S., Baudouin, C., Canal, P., Laurent, G., & Lautier, D. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.08.024 · Cited by 9
Metadata
- Authors
- Bharti, A., Kraeft, S.-K., Gounder, M., Pandey, P., Jin, S., Yuan, Z.-M., Lees-Miller, S. P., Weichselbaum, R., Weaver, D., Chen, L. B., Kufe, D., & Kharbanda, S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1998-11-01
- Volume
- 18
- Issue
- 11
- Pages
- 6719-6728
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2133991390
- Cited by
- 208
- References
- 0
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Inactivation of DNA-Dependent Protein Kinase by Protein Kinase Cδ: Implications for Apoptosis. https://app.cochat.ai/papers/10.1128/mcb.18.11.6719
- The paper
- Bharti, A., Kraeft, S.-K., Gounder, M., Pandey, P., Jin, S., Yuan, Z.-M., Lees-Miller, S. P., Weichselbaum, R., Weaver, D., Chen, L. B., Kufe, D., & Kharbanda, S. (1998). Inactivation of DNA-Dependent Protein Kinase by Protein Kinase Cδ: Implications for Apoptosis. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.18.11.6719
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