Elevation of cyclic AMP causes an imbalance between NF-κB and p53 in NALM-6 cells treated by doxorubicin
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We previously showed that cAMP can inhibit DNA damage-induced wild type p53 accumulation in human pre-B NALM-6 cells, leading to a profound reduction of their apoptotic response. Here, we provide evidence for the potentiation of DNA damage-induced NF-κB activation by cAMP. We found that inhibition of NF-κB activation prevents the inhibitory effect of cAMP on doxorubicin-induced apoptosis. Moreover, cAMP exerts its inhibitory effect on doxorubicin-induced apoptosis in a PKA-independent manner. The present study also shows that elevation of cAMP prolongs the phosphorylation of IκB and subsequent activation of NF-κB in doxorubicin treated NALM-6 cells in a proteasome-dependent manner. Taken together, our results demonstrate that cAMP abrogates the balance between apoptotic and antiapoptotic transcription factors that are hallmarks of DNA damage signaling. © 2010 Federation of European Biochemical Societies.