Back to Search
Start Over
Early adipogenesis is regulated through USP7-mediated deubiquitination of the histone acetyltransferase TIP60
- Source :
- Nature communications, 4. Nature Publishing Group
- Publication Year :
- 2013
- Publisher :
- Springer Science and Business Media LLC, 2013.
-
Abstract
- Transcriptional coregulators, including the acetyltransferase Tip60, have a key role in complex cellular processes such as differentiation. Whereas post-translational modifications have emerged as an important mechanism to regulate transcriptional coregulator activity, the identification of the corresponding demodifying enzymes has remained elusive. Here we show that the expression of the Tip60 protein, which is essential for adipocyte differentiation, is regulated through polyubiquitination on multiple residues. USP7, a dominant deubiquitinating enzyme in 3T3-L1 adipocytes and mouse adipose tissue, deubiquitinates Tip60 both in intact cells and in vitro and increases Tip60 protein levels. Furthermore, inhibition of USP7 expression and activity decreases adipogenesis. Transcriptome analysis reveals several cell cycle genes to be co-regulated by both Tip60 and USP7. Knockdown of either factor results in impaired mitotic clonal expansion, an early step in adipogenesis. These results reveal deubiquitination of a transcriptional coregulator to be a key mechanism in the regulation of early adipogenesis.
- Subjects :
- Male
Transcription, Genetic
Cellular differentiation
Mitosis
General Physics and Astronomy
Biology
Lysine Acetyltransferase 5
General Biochemistry, Genetics and Molecular Biology
Histones
Ubiquitin-Specific Peptidase 7
Transcriptome
Mice
3T3-L1 Cells
Adipocytes
Animals
RNA, Small Interfering
Histone Acetyltransferases
Regulation of gene expression
Adipogenesis
Multidisciplinary
Gene Expression Profiling
Ubiquitination
Cell Differentiation
General Chemistry
Histone acetyltransferase
Mice, Inbred C57BL
Adipose Tissue
Gene Expression Regulation
Biochemistry
Acetyltransferase
Trans-Activators
biology.protein
Ubiquitin-Specific Proteases
Protein Processing, Post-Translational
Signal Transduction
Deubiquitination
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....3cbf812f06e2c20ed9c3d0df7069c5cb