Functional properties of membrane-bound mucins MUC1 and MUC4 in the oral cavity
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MUCl and MUC4 are two membrane-bound mucins which are expressed on many epithelial surfaces throughout the body including the oral cavity. The functions of these mucins in normal cells are diverse, ranging from physiological roles in cell growth, differentiation, uterine embryo implantation, epithelial protection, bacterial attachment and signal transduction. In malignant cells, these mucins assume pathological roles in the masking of recognition sites for natural killer cells and promotion of tumor cell metastasis. Little is known, however, concerning the functions of these mucins in the oral cavity and the aims of this study were to (1) investigate the biosynthetic processing of MUCl and MUC4, (2) elucidate the protective functions of these mucins in oral epithelial cells in a model of bacterial injury and (3) to investigate the regulation of MUC 1 expression modulated by proinflammatory mediators and oral microorganisms. A series of MUCl and MUC4 expression constructs was prepared and used to investigate the biosynthetic processing of these two mucins. It was found that MUCl is cleaved into two subunits during the secretory pathway at the sequence FRPG/SVVV. Interestingly, nearly equal amounts of both full length uncleaved MUCl and the cleaved extracellular subunit of MUCl were found in COS-7 cells, suggesting that the cleavage event is part of a long term process, which may occur at different locations during secretion. In contrast, no evidence was found for a similar cleavage event during the biosynthesis of MUC4. This was surprising because the rat homologue of MUC4, SMC/Muc4 has been shown to undergo cleavage at the sequence Gly-Asp-Pro-His ... [TRUNCATED]
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact firstname.lastname@example.org.Thesis (D.Sc.D.)--Boston University Henry M. Goldman School of Dental Medicine, 2003 (Periodontology and Oral Biology).Includes bibliography (leaves 146-184).
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