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Role of a PKA Interacting Protein, AKIP, in Cell Signaling and Apoptosis
Author(s) -
Sastri Mira,
King Charles,
Taylor Susan S
Publication year - 2008
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.22.1_supplement.829.8
Subject(s) - transcription factor , protein subunit , microbiology and biotechnology , biology , protein kinase a , transcription (linguistics) , signal transduction , splice , phosphorylation , gene , chemistry , cancer research , biochemistry , linguistics , philosophy
A Kinase‐Interacting Protein/Breast Cancer Associated Gene 3 (AKIP/BCA3), a protein with three splice variants that is up‐regulated in breast cancers, was shown to bind the N‐terminus of the catalytic subunit of PKA (PKAc), and results in nuclear translocation of PKAc. AKIP/BCA3 is neddylated and can bind to and regulate NF‐κB‐dependent transcription. These findings suggest that AKIP/BCA3 functions as a molecular shuttle and direct regulator of transcription. Using a proteomics‐based approach, we identified Apoptosis Inducing Factor (AIF) and HSP‐70 as AKIP/BCA3 binding proteins. HSP‐70 has previously been shown bind and block nuclear translocation of AIF. Taken together, this suggests that AKIP/BCA3 acts a molecular shuttle for PKAc and AIF, but may be attenuated by HSP‐70. Our initial analysis of these protein:protein interactions revealed that PKAc, AIF, and HSP‐70 preferentially bind different splice variants of AKIP/BCA3. The two splice variants of AKIP/BCA3 up‐regulated in breast cancer could with pro‐survival proteins suggesting that an imbalance of AKIP/BCA3 import may significantly contribute to the pro‐survival signaling observed in breast cancer.