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Elevation of cyclic AMP causes an imbalance between NF‐κB and p53 in NALM‐6 cells treated by doxorubicin
Author(s) -
Safa Majid,
Zand Hamid,
Mousavizadeh Kazem,
Kazemi Ahmad,
Bakhshayesh Masoumeh,
Hayat Parisa
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.07.009
Subject(s) - doxorubicin , apoptosis , dna damage , phosphorylation , nf κb , transcription factor , proteasome , signal transduction , microbiology and biotechnology , kinase , chemistry , dna , biology , biochemistry , gene , chemotherapy , genetics
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.