Proteins that mediate the nuclear entry of the goat uterine estrogen receptor activation factor (E-RAF): Identification of a molecular basis for the inhibitory effect of progesterone on estrogen action

• Published in: Journal of cellular biochemistry Vol. 89; no. 1; pp. 108 - 119
• Main Authors: Govind, Anitha P., Sreeja, S., Thampan, Raghava Varman
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.05.2003
• Subjects: Active Transport, Cell Nucleus; Animals; Binding Sites; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Estradiol - metabolism; estrogen receptor activation factor; Estrogens - metabolism; Female; Goats; In Vitro Techniques; Models, Biological; Molecular Weight; Nuclear Localization Signals; Nuclear Pore - metabolism; nuclear pore complex protein; nuclear transport; Progesterone - metabolism; progesterone binding protein; Proteins - metabolism; RNA, Messenger - genetics; Transcription, Genetic; Uterus - metabolism
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.10482

A 66 kDa transport protein, tp66, has been identified as the protein that mediates the nuclear transport of the estrogen receptor activation factor (E‐RAF). Indirect evidence shows that tp66 influences the transport of E‐RAF mainly by recognizing the nuclear localization signals (NLS) on the latter. A 38 kDa nuclear pore complex protein (npcp38) has been identified to which tp66–E‐RAF complex gets ‘docked’ prior to the nuclear entry of E‐RAF. Progesterone binding to E‐RAF serves to dissociate E‐RAF from the tp66 thereby inhibiting the nuclear entry of E‐RAF. The demonstration of the high affinity progesterone binding property of E‐RAF adds credibility to the above findings. A change in conformation of E‐RAF being brought about by progesterone binding is evident from the results of the circular dichroism (CD) analysis. This appears to be the fundamental reason behind the dissociation of the tp66–E‐RAF complex under progesterone influence and provides a molecular basis for the estrogen ‘antagonistic’ action of progesterone. A nuclear run‐on transcription assay clearly demonstrates the transcription‐activation function of E‐RAF II, also reaffirming the functional role of tp66 in the nuclear entry of E‐RAF. J. Cell. Biochem. 89: 108–119, 2003. © 2003 Wiley‐Liss, Inc.