Nucleic Acids Research Advance Access originally published online on October 4, 2006
Nucleic Acids Research 2006 34(19):5552-5566; doi:10.1093/nar/gkl691
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2006, Vol. 34, No. 19 5552-5566
© 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 |
PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus
1 National Center of Biomedical Analysis Beijing 100850, China 2 Institute of Basic Medical Sciences Beijing 100850, China
*To whom correspondence should be addressed. Tel: +86 10 66930169; Fax: +86 10 68186281; Email: xmzhang{at}nic.bmi.ac.cn
Received June 16, 2006. Revised September 5, 2006. Accepted September 7, 2006.
Progesterone receptor (PR) plays a critical role in cell proliferation and differentiation, and its transcriptional activity is known to be modulated by cofactor proteins. In the present study, we demonstrated that in the presence of progesterone, protein inhibitor of activated STAT-3 (PIAS3) significantly inhibited the PR transcriptional activity and the expression of progesterone-responsive genes. Reduction of endogenous PIAS3 by PIAS3 small-interfering RNA enhanced PR transactivation in a ligand-dependent manner. PIAS3 interacted with PR both in vitro and in vivo and the interaction was enhanced by progesterone. Furthermore, our findings suggested that PIAS3 strongly induced PRB sumoylation at three sites, Lys-7, Lys-388 and Lys-531. In addition, novel roles in PRB nuclear retention and transactivation were identified for these sites. Our data also suggested that PIAS3 was recruited in a largely hormone-dependent manner in response to a progesterone-responsive promoter. Finally, we demonstrated that PIAS3 inhibited the DNA-binding activity of PR and influenced its nuclear export as well as PR transactivation. Taken together, these data strongly suggested that PIAS3 played an important physiological role in PR function.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. R. Daniel and C. A. Lange Protein kinases mediate ligand-independent derepression of sumoylated progesterone receptors in breast cancer cells PNAS, August 25, 2009; 106(34): 14287 - 14292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Pan, J. Zhao, W.-N. Zhang, H.-Y. Li, R. Mu, T. Zhou, H.-Y. Zhang, W.-L. Gong, M. Yu, J.-H. Man, et al. Induction of SOX4 by DNA damage is critical for p53 stabilization and function PNAS, March 10, 2009; 106(10): 3788 - 3793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Tremblay, B. J. Wilson, X.-J. Yang, and V. Giguere Phosphorylation-Dependent Sumoylation Regulates Estrogen-Related Receptor-{alpha} and -{gamma} Transcriptional Activity through a Synergy Control Motif Mol. Endocrinol., March 1, 2008; 22(3): 570 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Daniel, E. J. Faivre, and C. A. Lange Phosphorylation-Dependent Antagonism of Sumoylation Derepresses Progesterone Receptor Action in Breast Cancer Cells Mol. Endocrinol., December 1, 2007; 21(12): 2890 - 2906. [Abstract] [Full Text] [PDF]
|
|