CAND1 exchange factor promotes Keap1 integration into cullin 3-RING ubiquitin ligase during adipogenesis. 2015

Dawadschargal Dubiel, and Jürgen Ordemann, and Johann Pratschke, and Wolfgang Dubiel, and Michael Naumann
Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany. Electronic address: dawabo@charite.de.

Adipogenesis is governed by a plethora of regulatory proteins which are most commonly controlled by the ubiquitin proteasome system. Here, we show that the differentiation of LiSa-2 preadipocytes is associated with an increase of cullin-associated and neddylation-dissociated 1 (CAND1), COP9 signalosome (CSN), neddylated cullin 3 (Cul3) and the BTB protein Keap1. Silencing of CAND1 leads to a decrease and reduced integration of Keap1 into Cul3-RING ubiquitin ligases (CRL3) and to a retardation of adipogenesis. Transient transfection of LiSa-2 cells with CAND1 targeting miRNA148a also reduces Keap1 and slowed down adipogenesis of LiSa-2 cells. These results demonstrate for the first time that CAND1 acts as a BTB-protein exchange factor for CRL3 complexes. The specific increase of neddylated Cul3 might be explained by the recruitment of Cul3 or CRL3 in a membrane-bound location during adipogenesis. Together, the results show that during adipogenesis in LiSa-2 cells a CAND1-dependent remodeling and activation/neddylation of CRL3 complexes take place.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072019 Kelch-Like ECH-Associated Protein 1 An adaptor protein characterized by an N-terminal BTB-POZ DOMAIN and six KELCH REPEATS that functions as a substrate for the E3 UBIQUITIN LIGASE complex. It negatively-regulates NF-E2-RELATED FACTOR 2 by targeting it for ubiquitination and degradation by the PROTEASOME. It also represses genes regulated by ANTIOXIDANT RESPONSE ELEMENTS. KEAP-1 Protein,KEAP1 Protein,KEAP 1 Protein,Kelch Like ECH Associated Protein 1
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D044842 Cullin Proteins A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES. Cullin,Cullin Domain Protein,Cullin Domain Proteins,Cullin Protein,Cullins
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D047908 Intracellular Signaling Peptides and Proteins Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors. Intracellular Signaling Peptides,Intracellular Signaling Proteins,Peptides, Intracellular Signaling,Proteins, Intracellular Signaling,Signaling Peptides, Intracellular,Signaling Proteins, Intracellular
D050156 Adipogenesis The differentiation of pre-adipocytes into mature ADIPOCYTES. Adipogeneses
D034622 RNA Interference A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process. Gene Silencing, Post-Transcriptional,Post-Transcriptional Gene Silencing,Co-Suppression,Cosuppression,Posttranscriptional Gene Silencing,RNA Silencing,RNAi,Co Suppression,Gene Silencing, Post Transcriptional,Gene Silencing, Posttranscriptional,Gene Silencings, Posttranscriptional,Interference, RNA,Post Transcriptional Gene Silencing,Post-Transcriptional Gene Silencings,Silencing, Post-Transcriptional Gene

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