Cell Growth & Differentiation, Vol 6, Issue 12 1651-1658, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Involvement of stress-activated protein kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents

A Saleem, R Datta, ZM Yuan, S Kharbanda and D Kufe
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

The cellular response to 1-beta-D-arabinofuranosylcytosine (ara-C) includes activation of Jun/AP-1, induction of c-jun transcription, and programmed cell death. The stress-activated protein (SAP) kinases stimulate the transactivation function of c-jun by amino terminal phosphorylation. The present work demonstrates that ara-C activates p54 SAP kinase. The finding that SAP kinase is also activated by alkylating agents (mitomycin C and cisplatinum) and the topoisomerase I inhibitor 9-amino-camptothecin supports DNA damage as an initial signal in this cascade. The results demonstrate that ara-C also induces binding of SAP kinase to the SH2/SH3-containing adapter protein Grb2. SAP kinase binds to the SH3 domains of Grb2, while interaction of the p85 alpha-subunit of phosphatidylinositol 3-kinase complex. The results also demonstrate that ara-C treatment is associated with inhibition of lipid and serine kinase activities of PI 3-kinase. The potential significance of the ara-C-induced interaction between SAP kinase and PI 3-kinase is further supported by the demonstration that Wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. The finding that Wortmannin treatment is also associated with internucleosomal DNA fragmentation may support a potential link between PI 3-kinase and regulation of both SAP kinase and programmed cell death.

This article has been cited by other articles:

				S.-F. Chou, S.-W. Chang, and J.-L. Chuang Mitomycin C Upregulates IL-8 and MCP-1 Chemokine Expression via Mitogen-Activated Protein Kinases in Corneal Fibroblasts Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2009 - 2016. [Abstract] [Full Text] [PDF]

				I. M. Muller, V. M. Dirsch, A. Rudy, N. Lopez-Anton, G. R. Pettit, and A. M. Vollmar Cephalostatin 1 Inactivates Bcl-2 by Hyperphosphorylation Independent of M-Phase Arrest and DNA Damage Mol. Pharmacol., May 1, 2005; 67(5): 1684 - 1689. [Abstract] [Full Text] [PDF]

				K. Yoshida, Y. Miki, and D. Kufe Activation of SAPK/JNK Signaling by Protein Kinase Cdelta in Response to DNA Damage J. Biol. Chem., December 6, 2002; 277(50): 48372 - 48378. [Abstract] [Full Text] [PDF]

				D. Raina, N. Mishra, S. Kumar, S. Kharbanda, S. Saxena, and D. Kufe Inhibition of c-Abl with STI571 Attenuates Stress-Activated Protein Kinase Activation and Apoptosis in the Cellular Response to 1-beta -D-Arabinofuranosylcytosine Mol. Pharmacol., June 1, 2002; 61(6): 1489 - 1495. [Abstract] [Full Text] [PDF]

				T. A. Stadheim, N. Suh, N. Ganju, M. B. Sporn, and A. Eastman The Novel Triterpenoid 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) Potently Enhances Apoptosis Induced by Tumor Necrosis Factor in Human Leukemia Cells J. Biol. Chem., May 3, 2002; 277(19): 16448 - 16455. [Abstract] [Full Text] [PDF]

				K. Yoshida and D. Kufe Negative Regulation of the SHPTP1 Protein Tyrosine Phosphatase by Protein Kinase C delta in Response to DNA Damage Mol. Pharmacol., December 1, 2001; 60(6): 1431 - 1438. [Abstract] [Full Text] [PDF]

				X. A. Figueroa-Masot, M. Hetman, M. J. Higgins, N. Kokot, and Z. Xia Taxol Induces Apoptosis in Cortical Neurons by a Mechanism Independent of Bcl-2 Phosphorylation J. Neurosci., July 1, 2001; 21(13): 4657 - 4667. [Abstract] [Full Text] [PDF]

				D. Sampath and W. Plunkett The Role of c-jun Kinase in the Apoptotic Response to Nucleoside Analogue-induced DNA Damage Cancer Res., November 1, 2000; 60(22): 6408 - 6415. [Abstract] [Full Text]

				K. Yoshida, R. Weichselbaum, S. Kharbanda, and D. Kufe Role for Lyn Tyrosine Kinase as a Regulator of Stress-Activated Protein Kinase Activity in Response to DNA Damage Mol. Cell. Biol., August 1, 2000; 20(15): 5370 - 5380. [Abstract] [Full Text]

				S. Kharbanda, S. Saxena, K. Yoshida, P. Pandey, M. Kaneki, Q. Wang, K. Cheng, Y.-N. Chen, A. Campbell, T. Sudha, et al. Translocation of SAPK/JNK to Mitochondria and Interaction with Bcl-xL in Response to DNA Damage J. Biol. Chem., January 7, 2000; 275(1): 322 - 327. [Abstract] [Full Text] [PDF]

				W. D. Jarvis, C. R. Johnson, F. A. Fornari, J. S. Park, P. Dent, and S. Grant Evidence That the Apoptotic Actions of Etoposide Are Independent of c-Jun/Activating Protein-1-Mediated Transregulation J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1384 - 1392. [Abstract] [Full Text]

				R. A. Gjerset, S. Lebedeva, A. Haghighi, S. T. Turla, and D. Mercola Inhibition of the Jun Kinase Pathway Blocks DNA Repair, Enhances p53-mediated Apoptosis and Promotes Gene Amplification Cell Growth Differ., August 1, 1999; 10(8): 545 - 554. [Abstract] [Full Text]

				X. F. Hu, A. Slater, P. Kantharidis, D. Rischin, S. Juneja, R. Rossi, G. Lee, J. D. Parkin, and J. R. Zalcberg Altered Multidrug Resistance Phenotype Caused by Anthracycline Analogues and Cytosine Arabinoside in Myeloid Leukemia Blood, June 15, 1999; 93(12): 4086 - 4095. [Abstract] [Full Text] [PDF]

				W. D. Jarvis, F. A. Fornari Jr., R. M. Tombes, R. K. Erukulla, R. Bittman, G. K. Schwartz, P. Dent, and S. Grant Evidence for Involvement of Mitogen-Activated Protein Kinase, Rather than Stress-Activated Protein Kinase, in Potentiation of 1-beta -D-Arabinofuranosylcytosine-Induced Apoptosis by Interruption of Protein Kinase C Signaling Mol. Pharmacol., November 1, 1998; 54(5): 844 - 856. [Abstract] [Full Text]

				L. M. Martins, T. J. Kottke, S. H. Kaufmann, and W. C. Earnshaw Phosphorylated Forms of Activated Caspases Are Present in Cytosol From HL-60 Cells During Etoposide-Induced Apoptosis Blood, November 1, 1998; 92(9): 3042 - 3049. [Abstract] [Full Text] [PDF]

				S. Y. Fuchs, B. Xie, V. Adler, V. A. Fried, R. J. Davis, and Z.'e. Ronai c-Jun NH2-terminal Kinases Target the Ubiquitination of Their Associated Transcription Factors J. Biol. Chem., December 19, 1997; 272(51): 32163 - 32168. [Abstract] [Full Text] [PDF]

				H. Seimiya, T. Mashima, M. Toho, and T. Tsuruo c-Jun NH2-terminal Kinase-mediated Activation of Interleukin-1beta Converting Enzyme/CED-3-like Protease during Anticancer Drug-induced Apoptosis J. Biol. Chem., February 14, 1997; 272(7): 4631 - 4636. [Abstract] [Full Text] [PDF]

				P. Pandey, J. Raingeaud, M. Kaneki, R. Weichselbaum, R. J. Davis, D. Kufe, and S. Kharbanda Activation of p38 Mitogen-activated Protein Kinase by c-Abl-dependent and -independent Mechanisms J. Biol. Chem., September 27, 1996; 271(39): 23775 - 23779. [Abstract] [Full Text] [PDF]

				M C Hu, W R Qiu, X Wang, C F Meyer, and T H Tan Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. Genes & Dev., September 15, 1996; 10(18): 2251 - 2264. [Abstract] [PDF]