Phosphorylation and ubiquitination of the transcription factor sterol regulatory element-binding protein-1 in response to DNA binding
2006 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 281, no 35, 25278-25286 p.Article in journal (Refereed) Published
Members of the sterol regulatory element-binding protein (SREBP) family of transcription factors control cholesterol and lipid metabolism and play critical roles during adipocyte differentiation. The transcription factor SREBP1 is degraded by the ubiquitin-proteasome system following phosphorylation of Thr(426) and Ser(430) in its phosphodegron. We now demonstrate that the glycogen synthase kinase (GSK)-3beta-dependent phosphorylation of these residues in SREBP1 is enhanced in response to specific DNA binding. DNA binding enhances the direct interaction between the C-terminal domain of SREBP1 and GSK-3beta. Accordingly, we demonstrate that GSK-3beta is recruited to the promoters of SREBP target genes in vivo. As a result of the phosphorylation of Thr(426) and Ser(430), the ubiquitin ligase Fbw7 is recruited to SREBP molecules associated with target promoters. Using a reconstituted ubiquitination system, we demonstrate that Fbw7-mediated ubiquitination of SREBP1 is dependent on its DNA binding activity. Thus, DNA binding could provide a mechanistic link between the phosphorylation, ubiquitination, and degradation of active transcription factors.
Place, publisher, year, edition, pages
2006. Vol. 281, no 35, 25278-25286 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-81743DOI: 10.1074/jbc.M604983200ISI: 000240031300029PubMedID: 16825193OAI: oai:DiVA.org:uu-81743DiVA: diva2:109658