PMID: 11904304

 

    Legend: Gene, Sites

Title : Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins : alternative glycosylation/phosphorylation of THR-58 , a known mutational hot spot of c-Myc in lymphomas, is regulated by mitogens

Abstract :
  1. Previously, we reported that c-Myc is glycosylated by O-linked N-acetylglucosamine at Thr-58 , a known phosphorylation site and a mutational hot spot in lymphomas
  2. In this paper, we describe the production and characterization of two Thr-58 site-specific antibodies and use them to examine the modification of Thr-58 in living cells
  3. One antibody specifically reacts with the Thr-58-glycosylated form of c-Myc , and the other reacts only with unmodified Thr-58 in c-Myc
  4. Using these antibodies together with a commercial anti- Thr-58-phosphorylated c-Myc antibody, we simultaneously detected three forms of c-Myc ( Thr-58-unmodified, -phosphorylated, and -glycosylated)
  5. It has been reported that Thr-58 phosphorylation is dependent on a prior phosphorylation of Ser-62
  6. Mutagenesis of Ser-62 to Ala showed a marked decrease of Thr-58 phosphorylation and a marked increase of Thr-58 glycosylation
  7. Growth inhibition of HL60 cells by serum starvation increases Thr-58 glycosylation and correspondingly decreases its phosphorylation
  8. Serum stimulation has the opposite effect upon the modification status of Thr-58
  9. A candidate kinase responsible for Thr-58 phosphorylation is the glycogen synthase kinase 3 3 (GSK3)
  10. Lithium, a competitive inhibitor of GSK3, decreased Thr-58 phosphorylation and increased its glycosylation
  11. Finally, we show that the Thr-58-phosphorylated form of c-Myc predominantly accumulates in the cytoplasm rather than the nucleus upon inhibition of proteasome activity
  12. These data suggest that hierarchical phosphorylation of Ser-62 and Thr-58 and alternative glycosylation/phosphorylation of Thr-58 together regulate the myriad functions of c-Myc in cells
Output (sent_index, trigger, protein, sugar, site):
  • 0. O-glycosylation, , proteins, -, -
  • 1. Thr-58, , -, O-linked N-acetylglucosamine, Thr-58
  • 1. glycosylated, , c-Myc, -, -
  • 3. Thr-58-glycosylated, , form of c-Myc, -, -
  • 4. -glycosylated, , c-Myc, -, -
Output(Part-Of) (sent_index, protein, site):
  • 3. c-Myc, Thr-58
*Output_Site_Fusion* (sent_index, protein, sugar, site):
  • 1. c-Myc, O-linked N-acetylglucosamine, Thr-58

 

 

Protein NCBI ID SENTENCE INDEX
c-Myc 4609 0,1,3,4,12
form of c-Myc 4609 3,11