Evolution of the human MUC1 oncoprotein

Abstract

Abstract. The mucin (MUC) family consists of secreted and membrane-bound forms. The transmembrane mucin 1 (MUC1) is a heterodimer that is aberrantly overexpressed by diverse human carcinomas and certain hematologic malignancies. The MUC1 N-terminal (MUC1-N) and C-terminal (MUC1-C) subunits are generated by autocleavage within a SEA domain. The MUC1 cytoplasmic domain (MUC1-CD) located downstream of the SEA domain is sufficient for the induction of anchorage-independent growth and tumorigenicity; however, no information is available regarding the origin of these transforming sequences. Previous work demonstrated that, except for the SEA domain, MUC1 has no sequence homology with other membrane-bound mucins. The present results demonstrate that MUC1-CD evolved from repeat regions in the MUC5B secreted mucin. We also show that MUC1 sequences upstream to the SEA domain emerged from MUC5B. These findings indicate that both the MUC1-N and MUC1-C subunits evolved from secreted gel-forming mucins and that the MUC1-CD oncogenic function emerged by diversification after evolution from MUC5B.

miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death

“…1A). MUC1 homologs are restricted to mammalian species (34). Highly conserved putative miR-1226 response elements were found in the human MUC1 3'UTR and that of other vertebrates, indicating that miR-1226 may be of importance as a regulator of MUC1 expression (Fig.…”

Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1

“…This could lead to the upregulation of oncogenic targets of microRNAs and to constitutive activation of signaling that could increase invasion and migration activities. 35 Suh et al showed that miR-145 was regulated by DNA methylation in prostate cancer. 27 However, to our knowledge, there were no reports about low miR-145 expression associated with DNA methylation in NSCLC.…”

MUC1-C Oncoprotein Induces TCF7L2 Transcription Factor Activation and Promotes Cyclin D1 Expression in Human Breast Cancer Cells

“…Notably, the cyclin D1 gene is amplified in ϳ20% of human breast cancers (38), and the cyclin D1 protein is expressed at increased levels in ϳ50% of human breast tumors (39 -41). The human MUC1-C cytoplasmic domain is highly conserved in mice and other mammalian species (42). To determine whether inhibiting the MUC1-C cytoplasmic domain affects cyclin D1 expression, we used a cell-penetrating peptide, designated GO-201, which contains the CQCRRK sequence and blocks availability of the CQC motif for protein interactions (23,24).…”