Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 284, Issue 29, Pages 19248-19254Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.005678
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Funding
- National Key Basic Research [2006CB943704]
- National Natural Science Foundation for Distinguished Scholars [30625015]
- Program for Outstanding Medical Academic Leader [B-LJ06032]
- Shanghai Key Science and Technology Research Project [08dj1400603]
- National Natural Science Foundation [30700121]
- Shanghai Rising Star Program [08QA14012]
- National Institutes of Health [DK61671, HD13563]
- Shanghai Leading Academic Discipline [B110]
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CCAAT enhancer-binding protein (C/EBP)beta is a basic leucine zipper transcription factor family member, and can be phosphorylated, acetylated, and sumoylated. C/EBP beta undergoes sequential phosphorylation during 3T3-L1 adipocyte differentiation. Phosphorylation on Thr(188) by MAPK or cyclin A/cdk2 primes the phosphorylations on Ser(184)/Thr(179) by GSK3 beta, and these phosphorylations are required for the acquisition of DNA binding activity of C/EBP beta. Here we show that C/EBP beta is modified by O-GlcNAc, a dynamic single sugar modification found on nucleocytoplasmic proteins. 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. 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/EBP beta delayed the adipocyte differentiation program. Mutation of both Ser(180) and Ser(181) to Ala significantly increase the transcriptional activity of C/EBP beta. These data suggest that GlcNAcylation regulates both the phosphorylation and DNA binding activity of C/EBP beta.
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