Title : Alternative O-glycosylation/O-phosphorylation of the murine
estrogen receptor beta
Abstract :
- Estrogen receptor beta , a homologue to estrogen receptor alpha, is a new member of the steroid hormone receptor family
- Recently, we documented that estrogen receptor alpha, like other transcription factors , is modified by O-linked N-acetylglucosamine (O-GlcNAc), a ubiquitous transitory posttranslational modification on nuclear and cytoplasmic proteins
- Here, we report that estrogen receptor beta is alternatively modified by either O-GlcNAc or O-phosphate
- Lectin chromatography of in vitro translated protein first suggested that murine estrogen receptor beta ( mER-beta) is O-GlcNAcylated
- Structural characterization of the carbohydrate moieties on mER-beta, overexpressed in insect Sf9 cells, confirmed the presence of O-GlcNAc.
- mER-beta, overexpressed in mammalian cells, is also O-GlcNAcylated
- The major site of O-GlcNAc on mER-beta from Sf9 cells is Ser(16) near the N-terminus
- Concomitant analyses also documented the O-phosphorylation of mER-beta at Ser(16)
- MALDI-TOF mass spectrometry showed alternative occupancy of this locus by these two abundant and dynamic posttranslational modifications
- The localization of a major O-GlcNAc/O-phosphate site in proximity of the transactivation domain and as part of a PEST region (target sequences for rapid protein degradation) on mER-beta suggests that these modifications may play a role in regulating estrogen receptor beta transactivation and turnover