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CaM kinase I binds and regulates p53 in breast cancer cells (613.2)
Author(s) -
Geck Renee,
Schmitt John
Publication year - 2014
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.28.1_supplement.613.2
Subject(s) - cell cycle , cell growth , phosphorylation , kinase , mcf 7 , ionomycin , protein kinase a , cancer research , microbiology and biotechnology , cell cycle progression , chemistry , cell , cancer cell , biology , cancer , biochemistry , intracellular , genetics , human breast
P53 is a tumor suppressor protein that regulates gene expression and cell cycle progression. Calcium/calmodulin‐dependent protein kinase (CaM kinase) proteins, including CaM KK and CaM KI, are known to control ERK and several transcription factors. CaM KI has also been shown to bind and phosphorylate the cell cycle protein p27 to promote cell cycle progression. Interestingly, p53 contains a possible CaM KI phosphorylation site at S366. Our goal was to evaluate the ability of CaM KI to bind and regulate p53 as well as investigate its effects on p53 phosphorylation, the cell cycle, and cell growth in MCF‐7 and MDA‐MB‐231 breast cancer cells. GST pull‐downs showed that CaM KI associates with phosphorylated p53 at S366. Treatment of MCF‐7 cells with estrogen (E2) increases the endogenous association of CaM KI‐p53 as does treatment of MDA cells with the calcium‐elevating agent, ionomycin. None of the treatments led to an association of p53 with CaM KK, CaM KII, or CaM KIV. Interestingly, E2 increased MCF‐7 progression through the cell cycle and MCF‐7 cell growth, effects enhanced by inhibiting p53 with PFT‐α. In summary, our data suggests that CaM KI binds and phosphorylates p53 in MCF‐7 and MDA cells, and that E2 and PFT‐α stimulate MCF‐7 cell growth through a novel CaM KI‐p53 pathway. Grant Funding Source : Supported by M.J.Murdock Charitable Trust #2011267