An N-terminal Inhibitory Function, IF, Suppresses Transcription by the A-isoform but Not the B-isoform of Human Progesterone Receptors

The B-isoform of human progesterone receptors (PR) contains three activation functions (AF3, AF1, and AF2), two of which (AF1 and AF2) are shared with the A-isoform. AF3 is in the B-upstream segment (BUS), the far N-terminal 164 amino acids of B-receptors; AF1 is in the 392-amino acid N-terminal reg...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-03, Vol.273 (10), p.5455-5460
Main Authors: Hovland, Alicia Rudie, Powell, Roger L., Takimoto, Glenn S., Tung, Lin, Horwitz, Kathryn B.
Format: Article
Language:English
Subjects:
Gene Expression Regulation - genetics
HeLa Cells
Humans
Peptide Fragments - genetics
Peptide Fragments - pharmacology
Receptors, Estrogen - chemistry
Receptors, Estrogen - physiology
Receptors, Progesterone - chemistry
Receptors, Progesterone - physiology
Suppression, Genetic - physiology
Trans-Activators - chemistry
Trans-Activators - pharmacology
Transcription, Genetic - genetics
Transfection - genetics
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Summary:The B-isoform of human progesterone receptors (PR) contains three activation functions (AF3, AF1, and AF2), two of which (AF1 and AF2) are shared with the A-isoform. AF3 is in the B-upstream segment (BUS), the far N-terminal 164 amino acids of B-receptors; AF1 is in the 392-amino acid N-terminal region common to both receptors; and AF2 is in the C-terminal hormone binding domain. B-receptors are usually stronger transactivators than A-receptors due to transcriptional synergism between AF3 and one of the two downstream AFs. We now show that the N terminus of PR common to both isoforms contains an inhibitory function (IF) located in a 292-amino acid segment lying upstream of AF1. IF represses the activity of A-receptors but is not inhibitory in the context of B-receptors due to constraints imparted by BUS. As a result, IF inhibits AF1 or AF2 but not AF3, regardless of the position of IF relative to BUS. IF is functionally independent and strongly represses transcription when it is fused upstream of estrogen receptors. These data demonstrate the existence of a novel, transferable inhibitory function, mapping to the PR N terminus, which begins to assign specific roles to this large undefined region.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.10.5455