Cell surface-associated mucins in signal transduction

Abstract

Mucins are heavily glycosylated high molecular weight glycoproteins, which are involved in the protection and lubrication of luminal epithelial surfaces. Transmembrane mucins also engage in signal transduction, through extracellular domain-mediated ligand binding or by interacting with receptors for growth and differentiation factors. The cytoplasmic tail of MUC1 (MUC1CT), the best characterized of the transmembrane mucins, is involved in several signaling pathways, including those involving Ras, beta-catenin, p120 catenin, p53 and estrogen receptor alpha. MUC1CT also forms complexes with transcription factors, and then translocates to the nucleus by an unknown mechanism, where it is believed to influence the transcription of their target genes. MUC1CT has also been proposed to localize to mitochondrial membranes under conditions of genotoxic stress, where it attenuates the apoptotic pathway in response and confers resistance to apoptosis-inducing drugs.