scholarly journals The Protein Kinase Cδ Catalytic Fragment Is Critical for Maintenance of the G2/M DNA Damage Checkpoint

2009 ◽  
Vol 285 (3) ◽  
pp. 1879-1887 ◽  
Author(s):  
Edward L. LaGory ◽  
Leonid A. Sitailo ◽  
Mitchell F. Denning
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Checkpoint ◽  
Catalytic Fragment ◽  
Protein Kinase Cδ

scholarly journals p73β Is Regulated by Protein Kinase Cδ Catalytic Fragment Generated in the Apoptotic Response to DNA Damage

2002 ◽  
Vol 277 (37) ◽  
pp. 33758-33765 ◽  
Author(s):  
Jian Ren ◽  
Rakesh Datta ◽  
Hisashi Shioya ◽  
Yongqing Li ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Apoptotic Response ◽  
Catalytic Fragment ◽  
Protein Kinase Cδ

scholarly journals Activation of SAPK/JNK Signaling by Protein Kinase Cδ in Response to DNA Damage

2002 ◽  
Vol 277 (50) ◽  
pp. 48372-48378 ◽  
Author(s):  
Kiyotsugu Yoshida ◽  
Yoshio Miki ◽  
Donald Kufe
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Jnk Signaling ◽  
Protein Kinase Cδ

scholarly journals Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis

2011 ◽  
Vol 22 (8) ◽  
pp. 1398-1408 ◽  
Author(s):  
Choon-Ho Park ◽  
Bo-Hwa Choi ◽  
Min-Woo Jeong ◽  
Sangjune Kim ◽  
Wanil Kim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Protein Kinase ◽  
Cell Viability ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Regulatory Region ◽  
Dependent Manner ◽  
Protein Kinase Cδ

Vaccinia-related kinase 1 (VRK1) is a novel serine/threonine kinase that plays an important role in cell proliferation. However, little is known about the upstream regulators of VRK1 activity. Here we provide evidence for a role of protein kinase Cδ (PKCδ) in the regulation of murine VRK1. We show that PKCδ interacts with VRK1, phosphorylates the Ser-355 residue in the putative regulatory region, and negatively regulates its kinase activity in vitro. Intriguingly, PKCδ-induced cell death was facilitated by phosphorylation of VRK1 when cells were exposed to a DNA-damaging agent. In addition, p53 played a critical role in the regulation of DNA damage–induced cell death accompanied by PKCδ-mediated modulation of VRK1. In p53-deficient cells, PKCδ-mediated phosphorylation of VRK1 had no effect on cell viability. However, cells overexpressing p53 exhibited significant reduction of cell viability when cotransfected with both VRK1 and PKCδ. Taken together, these results indicate that PKCδ regulates phosphorylation and down-regulation of VRK1, thereby contributing to cell cycle arrest and apoptotic cell death in a p53-dependent manner.

rad-Dependent Response of the chk1-Encoded Protein Kinase at the DNA Damage Checkpoint

Science ◽  
1996 ◽  
Vol 271 (5247) ◽  
pp. 353-356 ◽  
Author(s):  
N. C. Walworth ◽  
R. Bernards
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Checkpoint

scholarly journals The Protein Kinase Cδ Catalytic Fragment Targets Mcl-1 for Degradation to Trigger Apoptosis

2006 ◽  
Vol 281 (40) ◽  
pp. 29703-29710 ◽  
Author(s):  
Leonid A. Sitailo ◽  
Shalini S. Tibudan ◽  
Mitchell F. Denning
Keyword(s):  
Protein Kinase ◽  
Catalytic Fragment ◽  
Protein Kinase Cδ

scholarly journals p38 Mitogen-Activated Protein Kinase Promotes Cell Survival in Response to DNA Damage but Is Not Required for the G2 DNA Damage Checkpoint in Human Cancer Cells

2010 ◽  
Vol 30 (15) ◽  
pp. 3816-3826 ◽  
Author(s):  
Mark S. Phong ◽  
Robert D. Van Horn ◽  
Shuyu Li ◽  
Gregory Tucker-Kellogg ◽  
Uttam Surana ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Human Cancer ◽  
Mitogen Activated Protein Kinase ◽  
Dna Damage Checkpoint ◽  
Checkpoint Control ◽  
Independent Manner ◽  
Bcl2 Family ◽  
Mitogen Activated Protein

ABSTRACT p38 mitogen-activated protein kinase (MAPK) is rapidly activated by stresses and is believed to play an important role in the stress response. While Chk1 is known to mediate G2 DNA damage checkpoint control, p38 was also reported to have an essential function in this checkpoint control. Here, we have investigated further the roles of p38 and Chk1 in the G2 DNA damage checkpoint in cancer cells. We find that although p38 activation is strongly induced by DNA damage, its activity is not required for the G2 DNA damage checkpoint. In contrast, Chk1 kinase is responsible for the execution of G2 DNA damage checkpoint control in p53-deficient cells. The inhibition of p38 activity has no effect on Chk1 activation and γ-H2AX expression. Global gene expression profiling of cancer cells in response to tumor necrosis factor alpha (TNF-α) revealed that p38 plays a strong prosurvival role through the coordinated downregulation of proapoptotic genes and upregulation of prosurvival genes. We show that the inhibition of p38 activity during G2 DNA damage checkpoint arrest triggers apoptosis in a p53-independent manner with a concurrent decrease in the level of Bcl2 family proteins. Our results suggest that although p38 MAPK is not required for the G2 DNA damage checkpoint function, it plays an important prosurvival role during the G2 DNA damage checkpoint response through the upregulation of the Bcl2 family proteins.

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