Title : A subpopulation of estrogen
receptors are modified by
O-linked N-acetylglucosamine.
Abstract :
- Estrogen receptors ( ER ) are ligand-inducible transcription factors regulated by Ser ( Thr )-O-phosphorylation
- Many transcription factors and eukaryotic RNA polymerase II itself are also dynamically modified by Ser Ser(Thr)-O-linked N-acetylglucosamine moieties (O-GlcNAc). Thr )-O-linked N-acetylglucosamine moieties (O-GlcNAc)
- Here we report that subpopulations of murine, bovine, and human estrogen receptors are modified by O-GlcNAc.
- O-GlcNAc moieties were detected on insect cell-expressed, mouse ER ( mER ) by probing with bovine milk galactosyltransferase , followed by structural analysis
- Wheat germ agglutinin-Sepharose affinity chromatography also readily detected terminal GlcNAc residues on subpopulations of ER purified from calf uterus, from human breast cancer cells (MCF-7), or from mER produced by in vitro translation
- These data suggest that greater than 10% of these populations of estrogen receptors bear O-GlcNAc.
- Site mapping of insect cell expressed mER localized one major site of O-GlcNAc addition to Thr-575 , within a PEST region of the carboxyl-terminal F domain
- Based upon their relative resistance to both hexosaminidase and to in vitro galactosylation, O-GlcNAc moieties appear to be largely buried on native mER
- This dynamic saccharide modification , like phosphorylation, may play a role in modulating the dimerization , stability, or transactivation functions of estrogen receptors