TY - JOUR
T1 - C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs
AU - Grooteclaes, Madeleine
AU - Deveraux, Quinn
AU - Hildebrand, Jeffrey
AU - Zhang, Qinghong
AU - Goodman, Richard H.
AU - Frisch, Steven M.
PY - 2003/4/15
Y1 - 2003/4/15
N2 - The genesis of carcinoma cells often involves epithelial-to-mesenchymal transitions and the acquisition of apoptosis resistance, but it is unclear whether these alterations are controlled coordinately or independently. Our previously reported effects of adenovirus E1a in human tumor cells raised the possibility that the E1a-interacting corepressor protein C-terminal-binding protein (CtBP) might selectively repress epithelial cell adhesion and proapoptotic genes. Here, we report that CtBP-knockout cells were hypersensitive to apoptosis. Correspondingly, microarray analysis of CtBP-knockout vs. CtBP-rescued mouse embryo fibroblasts revealed that many epithelial-specific and proapoptotic genes were indeed regulated by CtBP. Neither the apoptosis nor the repression activities of CtBP required histidine-315, suggesting that the proposed dehydrogenase activity is not essential for CtBP function. The results presented herein establish two functional roles of CtBP: to core-press epithelial genes, thus permitting epithelial-to-mesenchymal transitions, and to modulate the cellular threshold for apoptotic responses.
AB - The genesis of carcinoma cells often involves epithelial-to-mesenchymal transitions and the acquisition of apoptosis resistance, but it is unclear whether these alterations are controlled coordinately or independently. Our previously reported effects of adenovirus E1a in human tumor cells raised the possibility that the E1a-interacting corepressor protein C-terminal-binding protein (CtBP) might selectively repress epithelial cell adhesion and proapoptotic genes. Here, we report that CtBP-knockout cells were hypersensitive to apoptosis. Correspondingly, microarray analysis of CtBP-knockout vs. CtBP-rescued mouse embryo fibroblasts revealed that many epithelial-specific and proapoptotic genes were indeed regulated by CtBP. Neither the apoptosis nor the repression activities of CtBP required histidine-315, suggesting that the proposed dehydrogenase activity is not essential for CtBP function. The results presented herein establish two functional roles of CtBP: to core-press epithelial genes, thus permitting epithelial-to-mesenchymal transitions, and to modulate the cellular threshold for apoptotic responses.
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U2 - 10.1073/pnas.0830998100
DO - 10.1073/pnas.0830998100
M3 - Article
C2 - 12676992
AN - SCOPUS:0345352743
SN - 0027-8424
VL - 100
SP - 4568
EP - 4573
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -