Title :
c-Myc is glycosylated at
threonine 58 , a known phosphorylation
site and a mutational hot spot in lymphomas
Abstract :
- c-Myc is a helix-loop leucine zipper phosphoprotein that heterodimerizes with Max and regulates gene transcription in cell proliferation, cell differentiation, and programmed cell death
- Previously, we demonstrated that c-Myc is modified by O-linked N-acetylglucosamine (O-GlcNAc) within or nearby the N-terminal transcriptional activation domain (Chou, T.-Y., Dang, C.V., and Hart , G.W. ( 1995) Proc
- Natl. Acad
- Sci
- U.S.A. 92, 4417-4421)
- In this paper, we identified the O-GlcNAc attachment site(s) on c-Myc
- c-Myc purified from sf9 insect cells was trypsinized, and its GlcNAc moieties were enzymically labeled with [3H]galactose.
- The [3H]galactose-labeled glycopeptides were isolated by reverse phase high performance liquid chromatography and then subjected to gas-phase sequencing, manual Edman degradation, and laser desorption/ionization mass spectrometry
- These analyses show that threonine 58 , an in vivo phosphorylation site in the transactivation domain , is the major O-GlcNAc glycosylation site of c-Myc
- Mutation of threonine 58 , frequently found in retroviral v- Myc proteins and in human Burkitt and AIDS-related lymphomas, is associated with enhanced transforming activity and tumorigenicity
- The reciprocal glycosylation and phosphorylation at this biologically significant amino acid residue may play an important role in the regulation of the functions of c-Myc