Hovland A R, Powell R L, Takimoto G S, Tung L, Horwitz K B
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
J Biol Chem. 1998 Mar 6;273(10):5455-60. doi: 10.1074/jbc.273.10.5455.
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.
人孕激素受体（PR）的B亚型包含三种激活功能（AF3、AF1和AF2），其中两种（AF1和AF2）与A亚型共享。AF3位于B上游区段（BUS），即B受体N端最远端的164个氨基酸；AF1位于两种受体共有的392个氨基酸的N端区域；AF2位于C端激素结合域。由于AF3与两个下游AF之一之间的转录协同作用，B受体通常比A受体具有更强的反式激活能力。我们现在表明，两种亚型共有的PR的N端包含一种抑制功能（IF），位于AF1上游的一个292个氨基酸的区段内。IF抑制A受体的活性，但在B受体的情况下不具有抑制作用，这是由于BUS施加的限制。因此，无论IF相对于BUS的位置如何，IF都抑制AF1或AF2，但不抑制AF3。IF在功能上是独立的，当它融合在雌激素受体上游时，能强烈抑制转录。这些数据证明了一种新的、可转移的抑制功能的存在，该功能定位于PR的N端，这开始为这个大片未明确区域赋予特定的作用。
