Mapping and Characterization of the Functional Domains Responsible for the Differential Activity of the A and B Isoforms of the Human Progesterone Receptor

摘要: Abstract In humans, the biological response to progesterone is mediated by two distinct forms of receptor (human (h) PR-A, 94 kDa and hPR-B, 114 kDa). These isoforms are transcribed from estrogen-inducible promoters within a single copy PR gene; only difference between them that first 164 amino acids hPR-B (B-upstream sequence) absent in hPR-A. most cell lines such as MCF-7 breast cancer cells), CV-1 (monkey kidney fibroblasts), HeLa cervical carcinoma hPR-A functions transcriptional repressor, whereas activator progesterone-responsive genes. Interestingly, these contexts, also acts trans-dominant repressor activity other steroid hormone receptors. contrast hPR-A, which predominantly ligand-dependent we show this study A isoform chicken (cPR-A) lacks function all contexts examined. By constructing chimeras N-terminal domains human PR, mapped 140 protein. Notably, when 140-amino acid “repressor” domain placed onto latter changes repressor. however, “repressor domain” necessary, but not sufficient, for trans-repression it inactive tethered heterologous This suggests comprised requires context function. The identification discrete inhibitory region transferable another implies interacts with set transcription factors or adaptors those recognized will be required define mechanism modulates activity. Thus, although chickens humans both produce very similar receptor, clear studies action systems quite different.