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Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2003 Apr; Vol. 284 (4), pp. E830-40. Date of Electronic Publication: 2002 Dec 17. - Publication Year :
- 2003
-
Abstract
- Pancreatic duodenal homeobox-1 (Pdx1) is a transcription factor, and its phosphorylation is thought to be essential for activation of insulin gene expression. This phosphorylation is related to a concomitant shift in molecular mass from 31 to 46 kDa. However, we found that Pdx1 was modified by SUMO-1 (small ubiquitin-related modifier 1) in beta-TC-6 and COS-7 cells, which were transfected with Pdx1 cDNA. This modification contributed to the increase in molecular mass of Pdx1 from 31 to 46 kDa. Additionally, sumoylated Pdx1 localized in the nucleus. The reduction of SUMO-1 protein by use of RNA interference (SUMO-iRNAs) resulted in a significant decrease in Pdx1 protein in the nucleus. A 34-kDa form of Pdx1 was detected by the cells exposed to SUMO-iRNAs in the presence of lactacystin, a proteasome inhibitor. Furthermore, the reduced nuclear sumoylated Pdx1 content was associated with significant lower transcriptional activity of the insulin gene. These findings indicate that SUMO-1 modification is associated with both the localization and stability of Pdx1 as well as its effect on insulin gene activation.
- Subjects :
- Acetylcysteine pharmacology
Animals
COS Cells
Cell Nucleus metabolism
Cysteine Endopeptidases
Cysteine Proteinase Inhibitors pharmacology
Fibroblasts cytology
Fibroblasts metabolism
Gene Expression physiology
Humans
Multienzyme Complexes antagonists & inhibitors
Proteasome Endopeptidase Complex
Protein Processing, Post-Translational physiology
RNA, Double-Stranded pharmacokinetics
Transcription, Genetic physiology
Acetylcysteine analogs & derivatives
Homeodomain Proteins
Insulin genetics
SUMO-1 Protein genetics
SUMO-1 Protein metabolism
Trans-Activators genetics
Trans-Activators metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1849
- Volume :
- 284
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 12488243
- Full Text :
- https://doi.org/10.1152/ajpendo.00390.2002