title: 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.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yun-Chih
authors.initials: YC
authors.lastname: Tsai
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Tsai
authors.forename: Emily Yun-Chia
authors.initials: EY
authors.lastname: Chang
authors.forename: Siow-Wey
authors.initials: SW
authors.lastname: Hee
authors.forename: Wei-Hao
authors.initials: WH
authors.lastname: Chen
authors.forename: Sheng-Chung
authors.initials: SC
authors.lastname: Lee
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D015153:Blotting, Western; D019295:Computational Biology; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D051379:Mice; D008856:Microscopy, Fluorescence; D047495:PPAR gamma / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D014746:Vimentin / Q000378:metabolism*
chemical_list: D047495:PPAR gamma; D014746:Vimentin; D046988:Proteasome Endopeptidase Complex