title: PPARγ E3 ubiquitin ligase regulates MUC1-C oncoprotein stability.
abstract: MUC1-C oncoprotein is associated with colon, breast, ovarian, lung and pancreatic cancers. MUC1-C interacts with intracellular proteins to elicit signaling cascades that induce cell proliferation and tumor growth. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ), an E3 ubiquitin ligase, is an inhibitor of MUC1-C-mediated cell proliferation. PPARγ does so by binding to and inducing MUC1-C proteasome-dependent degradation that was independent of PPARγ transcriptional activity. Lys134 residue was found to be critically important for PPARγ-mediated MUC1-C degradation, as it terminated MUC1-C-mediated cell proliferation. These findings demonstrate PPARγ induces MUC1-C ubiquitination and degradation that is critical to terminate MUC1-C signaling pathway-elicited cancer.
authors.affiliation: Institute of Life Science, JiangSu University, Zhenjiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Institute of Life Science, JiangSu University, Zhenjiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.affiliation: Institute of Life Science, JiangSu University, Zhenjiang, China.
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.affiliation: Institute of Life Science, JiangSu University, Zhenjiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Life Science, JiangSu University, Zhenjiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Life Science, JiangSu University, Zhenjiang, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Institute of Life Science, JiangSu University, Zhenjiang, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation; D008239:Lysine; D061986:MCF-7 Cells; D018396:Mucin-1 / Q000502:physiology*; D015513:Oncogene Proteins / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D015398:Signal Transduction; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D015513:Oncogene Proteins; D047495:PPAR gamma; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D008239:Lysine