Regulatory Role of Glycogen Synthase Kinase 3 for Transcriptional Activity of ADD1/SREBP1c

Authors

Kang Ho Kim
Min Jeong Song
Eung Jae Yoo
Sung Sik Choe
Sang Dai Park
Jae Bum Kim

Publication Date

12-10-2004

Journal

Journal of Biological Chemistry

DOI

10.1074/jbc.M405522200

PMID

15466874

Abstract

Adipocyte determination- and differentiation-dependent factor 1 (ADD1) plays important roles in lipid metabolism and insulin-dependent gene expression. Because insulin stimulates carbohydrate and lipid synthesis, it would be important to decipher how the transcriptional activity of ADD1/SREBP1c is regulated in the insulin signaling pathway. In this study, we demonstrated that glycogen synthase kinase (GSK)-3 negatively regulates the transcriptional activity of ADD1/SREBP1c. GSK3 inhibitors enhanced a transcriptional activity of ADD1/SREBP1c and expression of ADD1/SREBP1c target genes including fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), and steroyl-CoA desaturase 1 (SCD1) in adipocytes and hepatocytes. In contrast, overexpression of GSK3beta down-regulated the transcriptional activity of ADD1/SREBP1c. GSK3 inhibitor-mediated ADD1/SREBP1c target gene activation did not require de novo protein synthesis, implying that GSK3 might affect transcriptional activity of ADD1/SREBP1c at the level of post-translational modification. Additionally, we demonstrated that GSK3 efficiently phosphorylated ADD1/SREBP1c in vitro and in vivo. Therefore, these data suggest that GSK3 inactivation is crucial to confer stimulated transcriptional activity of ADD1/SREBP1c for insulin-dependent gene expression, which would coordinate lipid and glucose metabolism.

Keywords

3T3-L1 Cells, Animals, Base Sequence, CCAAT-Enhancer-Binding Proteins, Cell Line, DNA, DNA-Binding Proteins, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Humans, In Vitro Techniques, Indoles, Insulin, Lipid Metabolism, Lithium Chloride, Maleimides, Mice, Phosphorylation, Rats, Recombinant Proteins, Signal Transduction, Sterol Regulatory Element Binding Protein 1, Transcription Factors, Transcription, Genetic

Published Open-Access

yes

Recommended Citation

Kim, Kang Ho; Song, Min Jeong; Yoo, Eung Jae; et al., "Regulatory Role of Glycogen Synthase Kinase 3 for Transcriptional Activity of ADD1/SREBP1c" (2004). Faculty, Staff and Student Publications. 4570.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4570