Biomedical subjects

Xiaolong Wei

Publications and source records attributed to Xiaolong Wei.

3 recordsLinked to original sources

PubMed2006

MUC1 oncoprotein stabilizes and activates estrogen receptor alpha.

The MUC1 protein is aberrantly overexpressed by most human breast carcinomas. We report that the MUC1 C-terminal subunit associates with estrogen receptor alpha (ERalpha) and that this interaction is stimulated by 17beta-estradiol (E2). MUC1 binds directly to the ERalpha DNA binding domain and stabilizes ERalpha by blocking its ubiquitination and degradation. Chromatin immunoprecipitation assays further demonstrate that MUC1 (1) associates with ERalpha complexes on estrogen-responsive promoters, (2) enhances ERalpha promoter occupancy, and (3) increases recruitment of the p160 coactivators SRC-1 and GRIP1. In concert with these results, we show that MUC1 stimulates ERalpha-mediated transcription and contributes to E2-mediated growth and survival of breast cancer cells. These findings provide evidence that MUC1 stabilizes ERalpha and that this oncoprotein is of importance to the activation of ERalpha function.

Antigens↗

PubMed2005

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.

Amino Acid Sequence↗

PubMed2003

Physical and functional interactions between PML and MDM2.

The tumor suppressor protein PML and oncoprotein MDM2 have opposing effects on p53. PML stimulates p53 activity by recruiting it to nuclear foci termed PML nuclear bodies. In contrast, MDM2 inhibits p53 by promoting its degradation. To date, neither a physical nor functional relationship between PML and MDM2 has been described. In this study, we report an in vivo and in vitro interaction between PML and MDM2 which is independent of p53. Two separate regions of PML are recognized which can interact with MDM2. The C-terminal half of PML, encoded by residues 300-633, can interact with the central region of MDM2 which includes the MDM2 acidic domain. In addition, PML amino acids 1-200, which encode the RING-finger and most of the B box zinc binding motifs, can interact with the C-terminal, RING-finger containing region of MDM2. Interestingly, PML mutants in which sumoylation at lysine 160 was inhibited displayed an increased association with MDM2, suggesting that sumoylation at this site may be a determinant of PML-MDM2 binding. Coexpression with MDM2 caused a redistribution of PML from the nucleus to the cytoplasm, and this required the PML N terminus and the MDM2 RING-finger domain. These results suggest that interaction between the PML N terminus and MDM2 C terminus can promote PML nuclear exclusion. Wild-type MDM2 inhibited the ability of PML to stimulate the transcriptional activity of a GAL4-CBP fusion protein. This inhibition required the central, acidic region of MDM2, but did not require the MDM2 C terminus. Taken together, these studies demonstrate that MDM2 and PML can interact through at least two separate protein regions, and that these interactions can have specific effects on the activity and/or localization of PML.

Animals↗