Nucleic Acids Research Advance Access originally published online on October 26, 2006
Nucleic Acids Research 2006 34(20):5974-5986; doi:10.1093/nar/gkl764
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2006, Vol. 34, No. 20 5974-5986
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
The molecular basis of the interaction between the proline-rich SH3-binding motif of PNRC and estrogen receptor alpha
Department of Surgical Research, Beckman Research Institute of City of Hope 1450 East Duarte Road, Duarte, CA 91010, USA
*To whom correspondence should be addressed. Tel: +1 626 359 8111, ext. 63454; Fax: +1 626 301 8972; Email: schen{at}coh.org
Received June 13, 2006. Revised September 9, 2006. Accepted September 27, 2006.
PNRC and PNRC2 are members of a new family of nuclear receptor coactivators. We systematically determined the molecular basis and the structure/function relationship for the PNRC–ER
interaction. PNRC was found to interact with ER mainly through its C-terminus region, amino acids 270–327, and an SH3-binding motif within this region was shown to be essential for PNRC to interact with and function as coactivator of ER. The importance of the flanking sequences of SH3-binding motif in the interaction between PNRC and ER was also investigated. The PNRC-interacting domain(s) on ER was also mapped. PNRC was found to interact with both AF1 and LBD of ER, and to function as a coactivator for both AF1 and AF2 transactivation functions. The interaction of ER mutants, I358R, K362A, V376R, L539R and E542K, with PNRC/PNRC2 was further investigated. ER/HBD/V376R could bind to PNRC or PNRC2, with similar affinity as wild-type ER/HBD, and the transactivation activity of ER/V376R was enhanced 5-fold by PNRC. Since GRIP1, a well-characterized coactivator, was found not to be able to enhance the transactivation function of this mutant, our results indicate that the PNRC–ER interaction interface is not exactly identical to that of GRIP1–ER interaction.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Zhang, B. Chen, Y. Li, J. Chen, G. Lou, M. Chen, and D. Zhou Transcriptional Regulation of the Human PNRC Promoter by NFY in HepG2 Cells J. Biochem., May 1, 2008; 143(5): 675 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rajhans, H. B. Nair, S. S. Nair, V. Cortez, K. Ikuko, N. B. Kirma, D. Zhou, A. E. Holden, D. W Brann, S. Chen, et al. Modulation of in Situ Estrogen Synthesis by Proline-, Glutamic Acid-, and Leucine-Rich Protein-1: Potential Estrogen Receptor Autocrine Signaling Loop in Breast Cancer Cells Mol. Endocrinol., March 1, 2008; 22(3): 649 - 664. [Abstract] [Full Text] [PDF]
|
|