TY - JOUR
T1 - Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2
AU - Mukhopadhyay, Debnath
AU - Houchen, Courtney W.
AU - Kennedy, Susan
AU - Dieckgraefe, Brian K.
AU - Anant, Shrikant
N1 - Funding Information:
The authors thank Nicholas Davidson, William F. Stenson, and Gustav Schonfeld for helpful discussions, Aubrey Morrison for the luciferase constructs, and Randal May and Karen Hutton for help with immunocytochemistry. This work was supported in part by NIH grants DK-52574 (B.K.D and S.A.), DK-02822 (C.W.H.), DK-60106 and AI-48137 (B.K.D.), and DK-62265 (S.A.). S.A. is a Research Scholar of the American Gastroenterology Association.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Cyclooxygenase-2 (COX-2) expression is translationally silenced in epithelial cells undergoing radiation-induced apoptosis. CUGBP2, a predominantly nuclear protein, is also rapidly induced in response to radiation and translocates to the cytoplasm. Antisense-mediated suppression of CUGBP2 renders radioprotection through a COX-2-dependent prostaglandin pathway, providing an in vivo demonstration of translation inhibition activity for CUGBP2. CUGBP2 binds to two sets of AU-rich sequences (AREs) located within the first sixty nucleotides of the COX-2 3′ untranslated region (3′UTR). Upon binding, CUGBP2 stabilizes a chimeric luciferase-COX-2 3′UTR mRNA but inhibits its translation. These findings identify a novel paradigm for RNA binding proteins in facilitating opposing functions of mRNA stability and translation inhibition and reveal a mechanism for inhibiting COX-2 expression in cancer cells.
AB - Cyclooxygenase-2 (COX-2) expression is translationally silenced in epithelial cells undergoing radiation-induced apoptosis. CUGBP2, a predominantly nuclear protein, is also rapidly induced in response to radiation and translocates to the cytoplasm. Antisense-mediated suppression of CUGBP2 renders radioprotection through a COX-2-dependent prostaglandin pathway, providing an in vivo demonstration of translation inhibition activity for CUGBP2. CUGBP2 binds to two sets of AU-rich sequences (AREs) located within the first sixty nucleotides of the COX-2 3′ untranslated region (3′UTR). Upon binding, CUGBP2 stabilizes a chimeric luciferase-COX-2 3′UTR mRNA but inhibits its translation. These findings identify a novel paradigm for RNA binding proteins in facilitating opposing functions of mRNA stability and translation inhibition and reveal a mechanism for inhibiting COX-2 expression in cancer cells.
UR - http://www.scopus.com/inward/record.url?scp=0037245474&partnerID=8YFLogxK
U2 - 10.1016/S1097-2765(03)00012-1
DO - 10.1016/S1097-2765(03)00012-1
M3 - Article
C2 - 12535526
AN - SCOPUS:0037245474
SN - 1097-2765
VL - 11
SP - 113
EP - 126
JO - Molecular cell
JF - Molecular cell
IS - 1
ER -