Evolution of the human MUC1 oncoprotein.
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.
Duraisamy
Sekhar
S
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Kufe
Turner
T
Ramasamy
Selvi
S
Kufe
Donald
D
D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D019143:Evolution, Molecular; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000235:genetics* / Q000502:physiology*; D055257:Mucin-5B; D009077:Mucins / Q000235:genetics; D010766:Phosphorylation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins
C524578:MUC5B protein, human; D018396:Mucin-1; D055257:Mucin-5B; D009077:Mucins; D011993:Recombinant Fusion Proteins