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Regulation of NF‐kB Nuclear Translocation by AKIP and PKAc
Author(s) -
King Charles C,
Sastri Mira,
Taylor Susan S.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.707.2
Subject(s) - chromosomal translocation , protein subunit , nuclear localization sequence , transcription (linguistics) , nf κb , transcription factor , nuclear transport , microbiology and biotechnology , chemistry , phosphorylation , nuclear protein , cell nucleus , nucleus , biology , gene , signal transduction , biochemistry , linguistics , philosophy
Regulation of NF‐?B Nuclear Translocation by AKIP and PKAcA K inase‐ I nteracting P rotein/ B reast C ancer A ssociated Gene 3 (AKIP/BCA3), a protein with three splice variants that is up‐regulated in breast cancers, binds the N‐terminus of the catalytic subunit of PKA (PKAc), and results in nuclear translocation of PKAc. Recent data has also demonstrated that AKIP/BCA3 binds NF‐?B and regulates transcription, suggesting that AKIP/BCA3 functions as a molecular shuttle for NF‐?B and a direct regulator of transcription. PKAc phosphorylates NF‐?B at serine 276, and can enhance nuclear translocation. Using a biochemical approach, the rate of GFP‐p65 nuclear translocation was monitored with different stimuli in the presence or absence of AKIP or a peptide that disrupts the interaction of AKIP and PKA. Enhanced nuclear translocation of p65 was observed in the presence of over‐expressed AKIP with TNFα and this could be blocked by the disrupting peptide. Addition of the cAMP analog (8‐CPT‐cAMP) was able to modestly induce p65 nuclear translocation in the absence of TNFα, and the combination of TNFα and 8‐CPT‐cAMP had a decreased rate of p65 nuclear translocation compared with TNFα alone. Taken together, these results suggest that AKIP regulates the rate of translocation of p65 into the nucleus in a PKA‐dependent manner.