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Cyclic AMP promotes cAMP-responsive element-binding protein-dependent induction of cellular inhibitor of apoptosis protein-2 and suppresses apoptosis of colon cancer cells through ERK1/2 and p38 MAPK.
J Biol Chem. 2004 Jun 18; 279(25):26176-83.JB

Abstract

We recently reported that cAMP suppresses apoptosis in colon cancer cells and induces cellular inhibitor of apoptosis protein-2 (c-IAP2) via a cAMP-responsive element (CRE), suggesting a mechanism for chemoprevention of colon cancer by non-steroidal anti-inflammatory drugs. In this study, we used T84 human colon cancer cells to define the pathway by which increases in cAMP induce c-IAP2 expression. Treatment with several different cAMP agonists stimulated phosphorylation of CRE-binding protein (CREB) and activated expression of c-IAP2 in a CREB-dependent manner. Studies with pharmacological inhibitors revealed that cAMP-dependent phosphorylation of CREB required activation of ERK1/2 and p38 MAPK but was largely independent of protein kinase A. Immunoblots and transcriptional reporter assays using specific inhibitors, as well as expression of constitutively active forms of MEK1 and MKK3, showed that c-IAP2 induction by cAMP is regulated predominantly through ERK1/2 and p38 MAPK and suggested involvement of p90 ribosomal protein S6 kinase and mitogen and stress response kinase-1 as well. Consistent with those results, we found that cAMP-dependent suppression of apoptosis was blocked by treatment with inhibitors of ERK1/2 and p38 MAPK. We conclude that cAMP can induce c-IAP2 expression in colon cancer cells through CREB phosphorylation and CRE-dependent transcription in a manner that involves activation of ERK1/2 and p38 MAPK. These results emphasize that activation of kinases other than protein kinase A can mediate the actions of agents that increase cAMP, particularly in the regulation of CREB-dependent events.

Authors+Show Affiliations

Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0636, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15078890

Citation

Nishihara, Hiroshi, et al. "Cyclic AMP Promotes cAMP-responsive Element-binding Protein-dependent Induction of Cellular Inhibitor of Apoptosis Protein-2 and Suppresses Apoptosis of Colon Cancer Cells Through ERK1/2 and P38 MAPK." The Journal of Biological Chemistry, vol. 279, no. 25, 2004, pp. 26176-83.
Nishihara H, Hwang M, Kizaka-Kondoh S, et al. Cyclic AMP promotes cAMP-responsive element-binding protein-dependent induction of cellular inhibitor of apoptosis protein-2 and suppresses apoptosis of colon cancer cells through ERK1/2 and p38 MAPK. J Biol Chem. 2004;279(25):26176-83.
Nishihara, H., Hwang, M., Kizaka-Kondoh, S., Eckmann, L., & Insel, P. A. (2004). Cyclic AMP promotes cAMP-responsive element-binding protein-dependent induction of cellular inhibitor of apoptosis protein-2 and suppresses apoptosis of colon cancer cells through ERK1/2 and p38 MAPK. The Journal of Biological Chemistry, 279(25), 26176-83.
Nishihara H, et al. Cyclic AMP Promotes cAMP-responsive Element-binding Protein-dependent Induction of Cellular Inhibitor of Apoptosis Protein-2 and Suppresses Apoptosis of Colon Cancer Cells Through ERK1/2 and P38 MAPK. J Biol Chem. 2004 Jun 18;279(25):26176-83. PubMed PMID: 15078890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclic AMP promotes cAMP-responsive element-binding protein-dependent induction of cellular inhibitor of apoptosis protein-2 and suppresses apoptosis of colon cancer cells through ERK1/2 and p38 MAPK. AU - Nishihara,Hiroshi, AU - Hwang,Michael, AU - Kizaka-Kondoh,Shinae, AU - Eckmann,Lars, AU - Insel,Paul A, Y1 - 2004/04/12/ PY - 2004/4/14/pubmed PY - 2004/7/24/medline PY - 2004/4/14/entrez SP - 26176 EP - 83 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 279 IS - 25 N2 - We recently reported that cAMP suppresses apoptosis in colon cancer cells and induces cellular inhibitor of apoptosis protein-2 (c-IAP2) via a cAMP-responsive element (CRE), suggesting a mechanism for chemoprevention of colon cancer by non-steroidal anti-inflammatory drugs. In this study, we used T84 human colon cancer cells to define the pathway by which increases in cAMP induce c-IAP2 expression. Treatment with several different cAMP agonists stimulated phosphorylation of CRE-binding protein (CREB) and activated expression of c-IAP2 in a CREB-dependent manner. Studies with pharmacological inhibitors revealed that cAMP-dependent phosphorylation of CREB required activation of ERK1/2 and p38 MAPK but was largely independent of protein kinase A. Immunoblots and transcriptional reporter assays using specific inhibitors, as well as expression of constitutively active forms of MEK1 and MKK3, showed that c-IAP2 induction by cAMP is regulated predominantly through ERK1/2 and p38 MAPK and suggested involvement of p90 ribosomal protein S6 kinase and mitogen and stress response kinase-1 as well. Consistent with those results, we found that cAMP-dependent suppression of apoptosis was blocked by treatment with inhibitors of ERK1/2 and p38 MAPK. We conclude that cAMP can induce c-IAP2 expression in colon cancer cells through CREB phosphorylation and CRE-dependent transcription in a manner that involves activation of ERK1/2 and p38 MAPK. These results emphasize that activation of kinases other than protein kinase A can mediate the actions of agents that increase cAMP, particularly in the regulation of CREB-dependent events. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15078890/Cyclic_AMP_promotes_cAMP_responsive_element_binding_protein_dependent_induction_of_cellular_inhibitor_of_apoptosis_protein_2_and_suppresses_apoptosis_of_colon_cancer_cells_through_ERK1/2_and_p38_MAPK_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15078890 DB - PRIME DP - Unbound Medicine ER -