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Designing Spatiotemporal Regulators for PKA in Prostate Cancer
Author(s) -
Kennedy Eileen J.,
Lewandowski Megan,
Hanold Laura,
Ton Norman,
Patel Fenil,
Patel Viral
Publication year - 2012
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.26.1_supplement.666.10
Subject(s) - prostate cancer , androgen receptor , protein kinase a , microbiology and biotechnology , androgen , signal transduction , transcription factor , context (archaeology) , scaffold protein , kinase , chemistry , cancer , biology , cancer research , biochemistry , genetics , hormone , gene , paleontology
A Kinase Interating Protein 1 (AKIP1) is highly upregulated in prostate cancer and can mislocalize Protein Kinase A (PKA) by translocating it from the cytoplasm to the nucleus. Further, AKIP1 acts as a scaffold to stabilize interactions between PKA and other proteins, thereby influencing PKA‐mediated signaling. PKA also plays an important role in late‐stage, androgen‐independent prostate cancer by promoting androgen‐dependent transcription and nuclear localization of the androgen receptor. While it is apparent that AKIP1 plays an important regulatory role for PKA, the specific changes that are mediated by AKIP1 in prostate cancer remain largely unknown. Therefore, it is of great importance to understand the biological implications of nuclear PKA activity and how this relates to androgen receptor localization and signaling in late‐stage prostate cancer. To address this, we have developed novel peptide‐based chemical biology tools that act to disrupt protein‐protein interactions as a means to interrogate AKIP1 activity in the context of prostate cancer cells. By applying these chemically stabilized compounds, we can elegantly and selectively disrupt interactions between PKA and AKIP1 while leaving the catalytic activity of PKA intact, thereby enabling us to interrogate the role of AKIP1 in prostate cancer as well as uncover its regulatory role on androgen receptor signaling.