Measuring the Dimerization Propensities of Mucin1 Transmembrane and Juxtamembrane Domains

Overexpression of the membrane protein mucin 1 (MUC1) has been linked to 75% of all human solid tumor cancers, including 90% of breast carcinomas. In cancer cells, MUC1-MUC1 homodimerization has been associated with cell migration and adhesion. Furthermore, this interaction is necessary for forming complexes with growth factor receptors and targeting to the nucleus, where MUC1 can interact with effector proteins regulating gene expression. Thus, understanding how MUC1 forms homodimers is essential for developing novel therapeutic strategies to block its oncogenic effects. A recent study has shown that the membrane proximal CQC motif promotes dimerization under oxidizing conditions, suggesting that the motif may act as a redox switch in response to changes of cytosolic oxidant levels. Aside from these few studies focusing on the CQC motif, very little is known regarding the mechanism of MUC1 homodimerization. Currently, we are using the ToxR and AraTM assays to investigate if the transmembrane domain, without the cytosolic CQC motif, is able to dimerize by itself. We are also measuring if the dimerization propensity of the TMD changes with the membrane proximal CQC motif. The two assays allow us to compare the dimerization propensity when the CQC motif is in reducing and oxidizing environments.