The inhibitory function in human progesterone receptor N termini binds SUMO-1 protein to regulate autoinhibition and transrepression - PubMed (original) (raw)
. 2002 Sep 13;277(37):33950-6.
doi: 10.1074/jbc.M204573200. Epub 2002 Jul 11.
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- PMID: 12114521
- DOI: 10.1074/jbc.M204573200
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The inhibitory function in human progesterone receptor N termini binds SUMO-1 protein to regulate autoinhibition and transrepression
Hany Abdel-Hafiz et al. J Biol Chem. 2002.
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Abstract
Although most studies of progesterone receptors (PR) and their two isoforms, PR-A and PR-B, focus on transcriptional stimulation, the receptors exhibit important inhibitory properties. Autoinhibition refers to an inhibitory function located in the PR N terminus, whose deletion increases transcriptional activity at least 6-10-fold. Transrepression refers to the ability of PR-A to suppress the transcriptional activity of PR-B and other nuclear receptors, including estrogen receptors. Self-squelching refers to the observation in transient transfection assays that increasing receptor concentrations paradoxically decrease transcriptional activity. Using a series of N-terminal deletion mutants constructed in both PR isoforms, we have mapped their autoinhibitory and transrepressor activities to a small ubiquitin-like modifier (SUMO-1) protein consensus-binding motif, (387)IKEE, located in the N terminus upstream of AF1. Self-squelching does not involve this site. SUMO-1 binds PR covalently at (387)IKEE, but only if the C-terminal, liganded, hormone-binding domain is also present. A single point K388R mutation within the (387)IKEE motif in either PR-A or PR-B leads to a loss of autoinhibitory and transrepressor functions of the liganded, full-length receptors. We conclude that autoinhibition and transrepression involve N-terminal sumoylation combined with intramolecular N/C-terminal communication.
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