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Dimerization of the Transmembrane Domain of Mucin 16
Author(s) -
Murphy Robert James,
Butch Nicole,
Li Edwin
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05340
Subject(s) - muc1 , mucin , transmembrane protein , cysteine , transmembrane domain , chemistry , microbiology and biotechnology , transcription factor , nucleus , biophysics , biochemistry , biology , gene , receptor , enzyme
Mucin 16 (MUC16) is a transmembrane protein produced by epithelial cells, and its main role is to contribute to the formation of a protective mucous barrier to inhibit debris, pathogens and viruses from entering the cells. However, when overexpressed, MUC16 can lead to cancers of the breast and ovary. Recent studies have shown that in cancer cells, MUC16 is trafficked to the nucleus, but little is known regarding the mechanism of this trafficking. One possible explanation may involve dimerization of MUC16, as shown in the case of mucin 1 (MUC1). Overexpression of the transmembrane MUC1 is also associated with various forms of cancer. Recent studies have shown that MUC1 is trafficked to the nucleus, where it may act as a transcription factor regulating the expression of genes associated with cell growth. The nuclear trafficking of MUC1 is dependent on the formation of MUC1 dimers, formed through inter‐disulfide bonds by two cysteine residues near the end of the transmembrane domain (TMD) of MUC1. The TMD of MUC16 (FWAVILIGLAGLLGVIT C LI C ) has two cysteine residues that reside in the end of the TMD, which led us to the hypothesis that MUC16 may also form cysteine‐mediated dimers. The ToxR assay, a technique to measure transmembrane domain dimerization, was used to investigate the roles of the cysteine residues in MUC16 TMD dimerization. Our preliminary results show that the cysteine residues in the TMD play a role in dimerization, but not as significant as in the case of MUC1 TMD. These results suggest that noncovalent interactions may be important for MUC16 TMD dimerization. Understanding the formation of MUC16 dimers, similar to MUC1, is important because dimerization may serve as a precursor to the nuclear trafficking of MUC16.