Cytoskeletal protein vimentin interacts with and regulates peroxisome proliferator‐activated receptor gamma via a proteasomal degradation process

Abstract

Peroxisome proliferators-activated receptor gamma (PPARγ) receptor is a transcription factor that is located in and functions primarily in the nucleus. PPARγ is exported from the nucleus upon mitogen and ligand stimulation under certain circumstances. However, a cytoplasmic PPARγ interacting protein and its function have not been previously identified. Here, we report for the first time that cytosolic PPARγ interacts directly with cytoskeletal vimentin. We performed PPARγ immunoprecipitation followed by mass spectrometry to identify the vimentin-PPARγ complex. This interaction was confirmed by reciprocal vimentin and PPARγ immunoprecipitation and co-immunofluorescence examination. We demonstrated that PPARγ colocalized with vimentin in certain organelles that is golgi, mitochondria, and endoplasmic reticulum. In cells depleted of vimentin, PPARγ was ubiquitinated and targeted to a proteasomal degradation pathway. Together, these findings indicate a direct interaction of PPARγ with vimentin in the cytosolic compartment, in which vimentin appears to play a role in regulating the turnover rate of PPARγ, which may further regulate genomic or non-genomic activities through the regulation of PPARγ protein degradation.

<p>Free Fatty Acids Promote the Development of Prostate Cancer by Upregulating Peroxisome Proliferator-Activated Receptor Gamma</p>

“…[52][53][54] Previous studies have found that vimentin interacts with PPARγ via a proteasomal degradation process. 55 Consequently, our results showed that PPARγ could promote the mRNA expression level of vimentin, while it could be reversed by the downregulation of PPARγ. The above results suggest that a high level of FFA may promote the expression of vimentin by upregulating PPARγ, which ultimately leads to the occurrence and development of PCa.…”

Heat-Killed Enterococcus faecalis Prevents Adipogenesis and High Fat Diet-Induced Obesity by Inhibition of Lipid Accumulation through Inhibiting C/EBP-α and PPAR-γ in the Insulin Signaling Pathway

“…During 3T3-L1 adipogenesis, C/EBP-α and PPAR-γ are activated by insulin with FBS in DM [ 27 , 28 ]. In addition, the experiments were conducted during adipogenesis to investigate how EF-2001 treatment regulates the expression level of transcription factors such as C/EBP-α and PPAR-γ.…”

STK38 is a PPARγ-interacting protein promoting adipogenesis

“…We next demonstrated that STK38 could significantly slow the degradation of PPARγ, but the underlying mechanism is not known at present. Nevertheless, the level of PPARγ protein has been reported to be regulated at multiple levels by SUMOylation and ubiquitination [ 14 , 15 ], ligand-binding [ 16 ], and also protein–protein interactions [ 17 ], which directly affect its activities. In this study, we found that PPARγ was quickly degraded, whereas STK38 levels remained relatively stable after inhibition of new protein synthesis by cycloheximide [ 18 ].…”