PMID: 19478079

 

    Legend: Sugar

Title : O-linked N-acetylglucosamine modification on CCAAT enhancer-binding protein beta : role during adipocyte differentiation

Abstract :

1. CCAAT enhancer-binding protein ( C/EBP)beta is a basic leucine zipper transcription factor family member, and can be phosphorylated, acetylated, and sumoylated
2. C/EBPbeta undergoes sequential phosphorylation during 3T3-L1 adipocyte differentiation
3. Phosphorylation on Thr(188) by MAPK or cyclin A / cdk2 primes the phosphorylations on Ser(184) /Thr(179) by GSK3beta , and these phosphorylations are required for the acquisition of DNA binding activity of C/EBPbeta
4. Here we show that C/EBPbeta is modified by O-GlcNAc, a dynamic single sugar modification found on nucleocytoplasmic proteins
5. The GlcNAcylation sites are Ser(180) and Ser(181) , which are in the regulation domain and are very close to the phosphorylation sites ( Thr(188), Ser(184), and Thr(179) ) required for the gain of DNA binding activity
6. Both in vitro and ex vivo experiments demonstrate that GlcNAcylation on Ser(180) and Ser(181) prevents phosphorylation on Thr(188), Ser(184), and Thr(179) , as indicated by the decreased relative phosphorylation and DNA binding activity of C/EBPbeta delayed the adipocyte differentiation program
7. Mutation of both Ser(180) and Ser(181) to Ala significantly increase the transcriptional activity of C/EBPbeta
8. These data suggest that GlcNAcylation regulates both the phosphorylation and DNA binding activity of C/EBPbeta