期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 107, 期 4, 页码 797-802出版社
WILEY
DOI: 10.1002/jcb.22177
关键词
Muc4; TGF beta; PROTEOSOME; REGULATION
资金
- National Institutes of Health [CA52498, EY12343]
- Sylvester Comprehensive Cancer Center of the University of Miami
Muc4 is a heterodimeric membrane mucin implicated in epithelial differentiation and tumor progression. It is expressed from a single gene as a 300 kDa precursor protein which is cleaved in the endoplasmic reticulum to its two subunits. Our previous work has shown that Muc4 is regulated by TGF beta, which represses the precursor cleavage. Working with Muc4-transfected A375 tumor cells, we now show that Muc4 undergoes proteosomal degradation. Proteosome inhibitors prolong the life of the precursor, shunt the Muc4 into cytoplasmic aggresomes, increase the level of Muc4 associated with the endoplasmic reticulum chaperones calnexin and calreticulin and increase the levels of ubiquitinated Muc4. Most importantly, proteosome inhibitors repress the TGF beta inhibition of Muc4 expression. These results suggest a model in which TGF beta inhibits precursor cleavage, shunting the precursor into the proteosomal degradation pathway. Thus, the cells have evolved a mechanism to use the quality control pathway for glycoproteins to control the quantity of the protein produced. J. Cell. Biochem. 107: 797802, 2009. (C) 2009 Wiley-Liss, Inc.
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