Regulation of adipocyte differentiation by clusterin-mediated Krüppel-like factor 5 stabilization
| Autor: | Eun-Sook Lee, Gukhan Kim, Bongkun Choi, Geun Hyang Kim, Jin Yoon, Seung-Whan Kim, Dong Seop Kim, Gyun-Sik Oh, Eun-Ju Chang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Transcriptional Activation Peroxisome proliferator-activated receptor gamma Ubiquitin-Protein Ligases Kruppel-Like Transcription Factors Biochemistry Cell Line 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation 3T3-L1 Cells CEBPA Genetics Adipocytes Animals Humans Promoter Regions Genetic Molecular Biology Transcription factor Gene knockdown Adipogenesis biology Clusterin Chemistry Ubiquitination Cell Differentiation Fibroblasts Ubiquitin ligase Cell biology Mice Inbred C57BL 030104 developmental biology biology.protein 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(12) |
| ISSN: | 1530-6860 |
| Popis: | Clusterin (CLU) is a heterodimeric glycoprotein involved in a range of biological processes. We investigated the function of CLU as a novel regulator of adipogenesis. CLU expression increased during 3T3-L1 preadipocyte differentiation. CLU overexpression promoted adipogenic differentiation of preadipocytes and increased the mRNA levels of adipogenic markers including peroxisome proliferator-activated receptor γ (Pparg) and CCAAT enhancer-binding protein α (Cebpa). Conversely, knockdown of CLU attenuated adipogenesis and reduced transcript levels of Pparg and Cebpa. However, the promoter activities of both the Pparg and the Cebpa gene were not affected by alteration of CLU expression on its own. Additionally, the protein level of Kruppel-like factor 5 (KLF5), an upstream transcription factor of Pparg and Cebpa involved in adipogenic differentiation, was upregulated by CLU overexpression, although the mRNA level of Klf5 was not altered by changes in the expression level of CLU. Cycloheximide chase assay showed that the increased level of KLF5 by CLU overexpression was due to decreased degradation of KLF5 protein. Interestingly, CLU increased the stability of KLF5 by decreasing KLF5 ubiquitination. CLU inhibited the interaction between KLF5 and F-box/WD repeat-containing protein 7, which is an E3 ubiquitin ligase that targets KLF5. The adipogenic role of CLU was also addressed in mesenchymal stem cells (MSCs) and Clu-/- mouse embryonic fibroblasts (MEFs). Furthermore, CLU enhanced KLF5-mediated transcriptional activation of both the Cebpa and the Pparg promoter. Taken together, these results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text