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 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.
Hovland
A R
AR
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Powell
R L
RL
Takimoto
G S
GS
Tung
L
L
Horwitz
K B
KB
D005786:Gene Expression Regulation / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000737:chemistry / Q000502:physiology; D011980:Receptors, Progesterone / Q000737:chemistry* / Q000502:physiology; D013489:Suppression, Genetic / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry / Q000494:pharmacology; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection / Q000235:genetics
D010446:Peptide Fragments; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015534:Trans-Activators