SERBP1 Is a Component of the Liver Receptor Homologue-1 Transcriptional Complex

Autor: Bruce D. Pascal, Ruben D. Garcia-Ordonez, Graham M. West, Yelenis Mari, Catherina Scharager-Tapia, Patrick R. Griffin
Rok vydání: 2015
Předmět:
Protein-Arginine N-Methyltransferases
Transcription
Genetic
Molecular Sequence Data
Receptors
Cytoplasmic and Nuclear
Biology
Chemical Fractionation
Transfection
Biochemistry
Article
Estrogen-related receptor alpha
Liver X receptor beta
Cell Line
Tumor
Humans
5-HT5A receptor
Amino Acid Sequence
RNA
Small Interfering
Nuclear Factor 90 Proteins
Promoter Regions
Genetic
Nuclear receptor co-repressor 1
Cell Nucleus
Liver receptor homolog-1
RNA-Binding Proteins
Molecular Sequence Annotation
General Chemistry
Molecular biology
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Recombinant Proteins
Neuron-derived orphan receptor 1
Nuclear receptor coactivator 1
Repressor Proteins
HEK293 Cells
Gene Expression Regulation
Proteolysis
Nuclear receptor coactivator 2
Hepatocytes
Peptides
Plasmids
Signal Transduction
Transcription Factors
Zdroj: Journal of proteome research. 14(11)
ISSN: 1535-3907
Popis: Liver receptor homolog-1 (LRH1) is an orphan nuclear receptor that has been shown to play a role in the transcriptional regulation of pathways involved in cancer. Elucidating the components of the LRH1 transcriptional complex to better understand endogenous regulation of the receptor as well as its role in cancer remains a high priority. A sub-cellular enrichment strategy coupled with proteomic approaches was employed to identify putative LRH1 coregulators. Nuclear fractionation protocol was essential for detection of LRH1 peptides by mass spectrometry (MS), with most peptides being observed in the insoluble fraction (receptor bound to DNA). SERBP1 and ILF3 were identified as LRH1 interacting partners by both western blot and MS/MS analysis. Receptor knockdown by siRNA showed an increased in SERBP1 expression while ILF3 expression was unchanged. In contrast, receptor overexpression decreased only SERBP1 mRNA levels. Consistent with these data, in a promoter:reporter assay, binding of LRH1 to the promoter region of SERBP1 resulted in a decrease in the expression level of the reporter gene, and subsequently, inhibiting transcription. Given the receptor’s role in cancer progression, the study here elucidates additional transcriptional machinery involved in LRH1 signaling and potentially provides new targets for therapeutics development.
Databáze: OpenAIRE
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