Cholesterol inhibits the nuclear entry of estrogen receptor activation factor (E-RAF) and its dimerization with the nonactivated estrogen receptor (naER) in goat uterus

Varman Thampan, Raghava ; Zafar, Atya ; Imam, N. S. ; Sreeja, S. ; Suma, K. ; Vairamani, M. (2000) Cholesterol inhibits the nuclear entry of estrogen receptor activation factor (E-RAF) and its dimerization with the nonactivated estrogen receptor (naER) in goat uterus Journal of Cellular Biochemistry, 77 (3). pp. 382-395. ISSN 0730-2312

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Official URL: http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1...

Related URL: http://dx.doi.org/10.1002/(SICI)1097-4644(20000601)77:3<382::AID-JCB4>3.0.CO;2-L

Abstract

An alternative form of estrogen receptor isolated from goat uterus, the nonactivated estrogen receptor (naER), has no DNA-binding function, although it is closely similar to the classical estrogen receptor (ER) in its hormone binding affinity and specificity. The naER dimerizes with a DNA binding protein, estrogen receptor activation factor (E-RAF). The heterodimer binds to the DNA. Assays carried out during the purification of E-RAF showed that an endogenous inhibitor that is heat stable and dialyzable bound to the E-RAF and prevented the formation of the heterodimer. The inhibitor has been isolated and purified. GC-MS analysis identifies this molecule to be cholesterol. Circular dichroism measurement has shown that the high-affinity binding of cholesterol to E-RAF results in subtle changes in the secondary and the tertiary structure of the protein. The E-RAF with altered conformation fails to dimerize with the naER. Instead of facilitating E-RAF entry into the nucleus, dimerization with the naER prevents it. Similarly, cholesterol binding blocks the nuclear entry of the protein, showing that E-RAF with altered conformation is incapable of interaction with the nuclear pore complex/membrane proteins. The naER-E-RAF heterodimer remains at the nuclear periphery, incapable of further transport. These results indicate the possibility that the dimerization between naER and the E-RAF takes place only within the nuclear compartment. The observation that cholesterol binding prevents nuclear entry of the E-RAF reflects the similarity of E-RAF with the sterol regulatory element (SRE) binding protein that enters the nucleus and binds to SRE only when the intracellular level of cholesterol remains low.

Item Type:Article
Source:Copyright of this article belongs to John Wiley & Sons.
Keywords:Cholesterol; Estrogen Receptor Activation Factor; Goat Uterus; Nonactivated Estrogen Receptor; Nuclear Migration
ID Code:55172
Deposited On:18 Aug 2011 12:12
Last Modified:18 Aug 2011 12:12

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