Role of the Transmembrane Domain of Mucin 1 in Nuclear Localization

Abstract

Mucin 1 (MUC1) is a highly glycosylated, single pass membrane protein that provides the mucous surfaces of epithelial cells and protects against pathogens. It consists of two parts, MUC1‐N, which includes the extracellular domain, and MUC1‐C, which includes the cytosolic and transmembrane domains. MUC1 overexpression has been observed in 80 to 90% of human solid tissue cancers. Studies have shown that this overexpression may lead to malignant unregulated gene expression when MUC1‐C enters the nucleus. The transport of MUC1‐C, from the plasma membrane to the nucleus, appears to be the result of MUC1‐C homodimerization. Our lab has utilized ToxR Assays to elucidate the role of the transmembrane domain in MUC1‐C dimerization. Using this assay we have seen that an Ala1180Leu mutation decreases the propensity of MUC1‐C to dimerize, implying it may be of importance to the dimer interface. Because this mutation is shown to decrease the ability of MUC1‐C to form dimers, the hypothesis is that it will also decrease the transport of MUC1‐C to the nucleus. Currently, we are working with mammalian (HEK) cells to determine if the Ala1180Leu mutation also affects nuclear localization of MUC1. Understanding of the mechanisms of MUC1‐C dimerization and nuclear localization is important in designing effective therapeutics.Support or Funding InformationSaint Joseph's University Department of Biology Saint Joseph's University Summer Scholars Program Edwin Li, Ph.D.