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Cytoplasmic translocation of p21 mediates NUPR1‐induced chemoresistance
Author(s) -
Vincent Andrew J.,
Ren Suping,
Harris Lillianne G.,
Devine Daniel J.,
Samant Rajeev S.,
Fodstad Oystein,
Shevde Lalita A.
Publication year - 2012
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.2012.07.063
Subject(s) - cancer research , phosphorylation , protein kinase b , cytoplasm , chromosomal translocation , breast cancer , apoptosis , triple negative breast cancer , biology , cancer , microbiology and biotechnology , medicine , gene , genetics
The expression of Nuclear Protein 1 (NUPR1) is associated with chemoresistance in multiple malignancies. We previously reported that NUPR1 functions as a transcriptional cofactor for the p300–p53 complex and transcriptionally regulates p21 expression. In the present study we investigated the activity of NUPR1 in p53‐deficient, triple‐negative, inflammatory SUM159 breast cancer cells. Our studies reveal that NUPR1 confers growth benefit and chemoresistance by causing Akt‐mediated phosphorylation and subsequent cytoplasmic re‐localization of p21 and activation of the anti‐apoptotic Bcl‐xL protein. Our findings elucidate a NUPR1‐PI‐3‐K/Akt‐phospho‐p21 axis that functions in p53‐negative, inflammatory breast cancer cells to enhance chemoresistance in breast cancer.