REGULATION OF MUCIN GLYCOPROTEIN BIOSYNTHESIS

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The purpose of this investigation is to study the mechanisms which regulate the biosynthesis and cellular processing of mucin-glycoproteins. In particular, we are interested in examining how these processes are influenced by normal physiological development. The transcription of the mRNA which directs the synthesis of these mucins will be studied by analyzing the biosynthesis of these specific messengers and quantitating their levels by hybridization to the appropriate cDNA probes. The course of mucin mRNA translation will be assessed by immunochemical quantitation of the newly synthesized peptide (apo-mucin) using antiserum of known specificity to the peptide core. Lastly, post-translational modification of the apo-mucins will be studied. First we will determine if apo-mucin is synthesized with a signal sequence is present (i.e.: pre-apo-mucin). In addition, we will attempt to identify the structural and conformational determinants which influence glycosylation of the apo-mucin. Finally, we will quantitate the levels of specific oligosaccharides and map their position on the peptide backbone, to determine if these parameters vary with normal, physiological development.