Control of Smad7 stability by competition between acetylation and ubiquitination
2002 (English)In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 10, no 3, 483-493 p.Article in journal (Refereed) Published
Smad proteins regulate gene expression in response to TGFbeta signaling. Here we present evidence that Smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of Smad7 on two lysine residues in its N terminus. Acetylation or mutation of these lysine residues stabilizes Smad7 and protects it from TGFbeta-induced degradation. Furthermore, we demonstrate that the acetylated residues in Smad7 also are targeted by ubiquitination and that acetylation of these lysine residues prevents subsequent ubiquitination. Specifically, acetylation of Smad7 protects it against ubiquitination and degradation mediated by the ubiquitin ligase Smurf1. Thus, our data suggest that competition between ubiquitination and acetylation of overlapping lysine residues constitutes a novel mechanism to regulate protein stability.
Place, publisher, year, edition, pages
2002. Vol. 10, no 3, 483-493 p.
Acetylation, Activin Receptors; Type I/genetics/metabolism, Amino Acid Sequence, Animals, Cell Line, DNA-Binding Proteins/genetics/*metabolism, Humans, Ligases/metabolism, Lysine/*metabolism, Molecular Sequence Data, Mutation, Nuclear Proteins/genetics/*metabolism, Protein Binding, Proto-Oncogene Proteins c-myc/genetics/metabolism, Receptors; Transforming Growth Factor beta/genetics/metabolism, Recombinant Fusion Proteins/genetics/metabolism, Signal Transduction/physiology, Smad7 Protein, Trans-Activators/genetics/*metabolism, Transforming Growth Factor beta/*metabolism, Ubiquitin/*metabolism, Ubiquitin-Protein Ligases
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-10404DOI: 10.1016/S1097-2765(02)00639-1PubMedID: 12408818OAI: oai:DiVA.org:uu-10404DiVA: diva2:38172