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MUC1 Expression Is Repressed by Protein Inhibitor of Activated Signal Transducer and Activator of Transcription-y

Department of Reproductive Medicine (M.J.B.), University of California, San Diego, School of Medicine, La Jolla, California 92093; Department of Biological Sciences (N.D., D.D.C.), University of Delaware, Newark, Delaware 19716; and Ordway Research Institute (E.L.), Cancer Center, Albany, New York 12208

Address all correspondence and requests for reprints to: Daniel D. Carson, Ph.D., Department of Biological Sciences, University of Delaware, 118C Wolf Hall, Newark, Delaware 19713. E-mail: dcarson{at}udel.edu.

Mucin 1 (MUC1) is a transmembrane glycoprotein that modulates the interaction between the embryo and the uterine epithelial cell surface. MUC1 also is a tumor marker and has been implicated in the protection of cancer cells from immune cell attack as well as in cell signaling in some tumors. We and others have shown that MUC1 expression is activated by progesterone (P), TNF-, and interferon- (IFN-). Here we demonstrate that MUC1 expression is down-regulated by overexpression of members of the protein inhibitor of activated signal transducer and activator of transcription (PIAS) family, PIAS1, PIAS3, PIASx, PIASxß, and PIASy, in human uterine epithelial cell lines HES and HEC-1A and in a breast cancer cell line, T47D. Treatments with P, TNF-, and IFN- were unable to overcome the repression by PIASy. PIASy repression of basal, P-, and TNF--stimulated MUC1 promoter activity was not dependent on the PIASy sumoylation domain. In contrast, PIASy suppression of IFN--activated MUC1 promoter activity was dependent on the PIASy sumoylation domain. PIASy and P receptor B were localized to the nucleus upon P treatment, and small interfering RNA knockdown of PIASy resulted in an increase in P-mediated stimulation of MUC1 protein expression. Overexpression of PIASy did not affect P receptor B binding to the MUC1 promoter but surprisingly led to a loss of nuclear receptor corepressor (NCoR), which was recruited to the promoter in response to P. Collectively, these data indicate that PIASy may be a useful target for down-regulation of MUC1 expression in various contexts.

NURSA Molecule Pages Link:

Nuclear Receptors:   PR

Coregulators:   ARIP3  |  PIAS1  |  PIAS3  |  PIAS4  |  SRC-1  |  AIB1  |  NCOR  |  SMRT

Ligands:   Progesterone  |  R5020

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