Evolution of the human MUC1 oncoprotein

Int J Oncol. 2007 Sep;31(3):671-7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cytoplasm / metabolism
  • Dimerization
  • Evolution, Molecular
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Models, Genetic
  • Molecular Sequence Data
  • Mucin-1 / genetics*
  • Mucin-1 / physiology*
  • Mucin-5B
  • Mucins / genetics
  • Phosphorylation
  • Phylogeny
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins

Substances

  • MUC5B protein, human
  • Mucin-1
  • Mucin-5B
  • Mucins
  • Recombinant Fusion Proteins