Human MUC1 oncoprotein regulates p53-responsive gene transcription in the genotoxic stress response.
The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas. The present work demonstrates that MUC1 associates with the p53 tumor suppressor, and that this interaction is increased by genotoxic stress. The MUC1 cytoplasmic domain binds directly to p53 regulatory domain. Chromatin immunoprecipitation assays demonstrate that MUC1 coprecipitates with p53 on the p53-responsive elements of the p21 gene promoter and coactivates p21 gene transcription. Conversely, MUC1 attenuates activation of Bax transcription. In concert with these results, MUC1 promotes selection of the p53-dependent growth arrest response and suppresses the p53-dependent apoptotic response to DNA damage. These findings indicate that MUC1 regulates p53-responsive genes and thereby cell fate in the genotoxic stress response.
Wei
Xiaolong
X
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Xu
Hai
H
Kufe
Donald
D
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D015536:Down-Regulation; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008957:Models, Genetic; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002843:Chromatin; D018396:Mucin-1; D016159:Tumor Suppressor Protein p53; D005982:Glutathione Transferase