ArticleThe Journal of biological chemistry2013
PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Glucose-Responsive PAGR1-Regulated Skeletal Muscle Gene Program Controls Systemic Glucose Homeostasis and Hepatic Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PTIP-Associated Protein 1: More Than a Component of the MLL3/4 Complex.Frontiers in genetics · 2022Review
- Dissecting transcriptional amplification by MYC.eLife · 2020Article
- An Approach to Greater Specificity for Glucocorticoids.Frontiers in endocrinology · 2018Review
- Kinetically Defined Mechanisms and Positions of Action of Two New Modulators of Glucocorticoid Receptor-regulated Gene Induction.The Journal of biological chemistry · 2016Article
- Kinetically-defined component actions in gene repression.PLoS computational biology · 2015Article
- Article
- Prenatal expression patterns of genes associated with neuropsychiatric disorders.The American journal of psychiatry · 2014Article
- Research resource: modulators of glucocorticoid receptor activity identified by a new high-throughput screening assay.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Loss of function of mouse Pax-Interacting Protein 1-associated glutamate rich protein 1a (Pagr1a) leads to reduced Bmp2 expression and defects in chorion and amnion development.Developmental dynamics : an official publication of the American Association of Anatomists · 2014Article
- A kinase-independent activity of Cdk9 modulates glucocorticoid receptor-mediated gene induction.Biochemistry · 2014Article
- Minireview: dynamic structures of nuclear hormone receptors: new promises and challenges.Molecular endocrinology (Baltimore, Md.) · 2014Review
- A conserved protein motif is required for full modulatory activity of negative elongation factor subunits NELF-A and NELF-B in modifying glucocorticoid receptor-regulated gene induction properties.The Journal of biological chemistry · 2013Article
- Variable steroid receptor responses: Intrinsically disordered AF1 is the key.Molecular and cellular endocrinology · 2013Review
- PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.PloS one · 2013Article
- Theory of partial agonist activity of steroid hormones.AIMS molecular scienceArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (A(max)), the potency of agonists (EC(50)), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.