Related Experiment Video
Updated: Jun 27, 2026
10:51
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
PIASy inhibits LRH-1-dependent CYP11A1 expression by competing for SRC-1 binding
Hsiang-Tsan Hsieh1, Chih-Hung Wang, Mei-Ling Wu
1Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
The Biochemical Journal
|December 11, 2008
Summary
Protein inhibitor of activated STAT y (PIASy) represses liver receptor homolog-1 (LRH-1) activity by competing with co-activators. This study elucidates PIASy
Area of Science:
- Molecular endocrinology
- Nuclear receptor signaling
- Steroidogenesis
Background:
- Liver receptor homolog-1 (LRH-1) is an orphan nuclear receptor crucial for development, bile acid synthesis, cholesterol metabolism, and ovarian steroid hormone production.
- LRH-1 regulates steroidogenic genes in the ovary, impacting steroid hormone synthesis.
Purpose of the Study:
- To investigate the molecular mechanisms by which PIASy represses LRH-1-mediated transcriptional activation of the CYP11A1 gene.
- To determine the role of SUMOylation and co-activator interaction in PIASy-mediated repression of LRH-1.
Main Methods:
- Investigated LRH-1 transactivation of the CYP11A1 promoter.
- Utilized immunoprecipitation and mammalian two-hybrid assays to study protein interactions.
- Assessed the impact of PIASy and SRC-1 on LRH-1 activity and CYP11A1 promoter induction.
Main Results:
- PIASy significantly repressed LRH-1-mediated transactivation of the CYP11A1 promoter.
- PIASy-mediated repression was independent of LRH-1 SUMOylation and did not involve histone deacetylase activity.
- PIASy interacted with LRH-1's C-terminal region, including the AF-2 motif, and inhibited SRC-1 binding.
- Overexpression of SRC-1 partially rescued PIASy-induced repression.
Conclusions:
- PIASy represses LRH-1 activity primarily through competition with co-activators like SRC-1.
- This competitive mechanism is crucial for understanding PIASy's role in regulating LRH-1-mediated gene transcription, particularly in steroidogenesis.
Related Concept Videos
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:12GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...