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The Roles of the Juxtamembrane Cysteine and Glutamine Residues in Mucin 1 (MUC1) Dimerization
Author(s) -
Li Edwin,
Herrera Roberto,
Cani Ksandros,
Freeman Christina
Publication year - 2018
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.2018.32.1_supplement.815.2
Subject(s) - muc1 , cysteine , transmembrane domain , transmembrane protein , alanine , glutamine , mucin , chemistry , biochemistry , amino acid , biology , microbiology and biotechnology , receptor , enzyme
Mucin 1 (MUC1) is an O‐glycosylated transmembrane protein involved in forming protective mucous barriers on epithelial cells that line the mucosal surfaces of different tissues including breast, stomach, pancreas, and lung. When this protein is overexpressed, MUC1 dimerizes through the formation of disulfide bonds. A MUC1 fragment is then cleaved and transported to the nucleus, where it regulates apoptotic genes that allow for tumorigenesis. The CQC motif, located in the juxtamembrane domain of MUC1, has been shown to be important for dimerization to occur. However, the importance of the position of the CQC motif and the roles of the glutamine and each cysteine residues remain unclear. To answer these questions, we have been using the ToxR assay to measure beta‐galactosidase activity as a reporter of transmembrane dimerization. In this assay, we use a chimeric protein that contains the transmembrane domain and the juxtamembrane CQC motif of MUC1. To investigate the relevance of the position of the cysteines with respect to each other within the CQC motif, we have inserted an alanine before the glutamine (CAQC). To determine the role of the glutamine residue in dimerization, we have exchanged it for an alanine (CAC). Furthermore, to study the contribution of each cysteine, we have substituted the cysteine residues with alanine (CQA, AQC, and AQA). By providing additional information about the role of the CQC motif in dimerization we will further our knowledge about the mechanism of the MUC1 pathway that is involved in cancer. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .