Post-translational regulation of CD133 by ATase1/ATase2-mediated lysine acetylation

J Mol Biol. 2014 May 29;426(11):2175-82. doi: 10.1016/j.jmb.2014.02.012. Epub 2014 Feb 17.


The CD133 cell-surface protein expresses the AC133 epitope that is associated with cancer progenitor cells and cancer resistance to traditional anticancer therapies. We report that the endoplasmic reticulum Golgi intermediate compartment residing acetyltransferases, ATase1 (NAT8B) and ATase2 (NAT8), can physically interact with CD133 to acetylate the protein on three lysine residues predicted to reside on the first extracellular loop of CD133. Site-directed mutagenesis of these residues mimicking a loss of acetylation and downregulation or inhibition of ATase1/ATase2 resulted in near-complete abolishment of CD133 protein expression. We also demonstrate that targeting ATase1/ATase2 results in apoptosis of CD133 expressing acute lymphoblastic leukemia cells. Taken together, we suggest that lysine acetylation on predicted extracellular residues plays a key role in expression and trafficking of CD133 protein to the cell surface and can be targeted to disrupt CD133 regulation and function.

Keywords: ERGIC; membrane protein; post-translation modifications; protein processing; trafficking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Acetylation / drug effects
  • Acetyltransferases / antagonists & inhibitors
  • Acetyltransferases / metabolism*
  • Amino Acid Sequence
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Caco-2 Cells
  • Enzyme Inhibitors / pharmacology
  • Gene Expression
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • HEK293 Cells
  • Humans
  • Lysine / genetics
  • Lysine / metabolism*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptides / genetics
  • Peptides / metabolism*
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Transport
  • Tumor Cells, Cultured


  • AC133 Antigen
  • Antigens, CD
  • Enzyme Inhibitors
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Acetyltransferases
  • NAT8 protein, human
  • Lysine