Nucleic Acids Research, 2001, Vol. 29, No. 19 3939-3948
© 2001 Oxford University Press
PNRC2 is a 16 kDa coactivator that interacts with nuclear receptors through an SH3-binding motif
Division of Immunology, Beckman Research Institute of the City of Hope, 1450 East Duarte Road, Duarte, CA 91010, USA
PNRC2 (proline-rich nuclear receptor co-regulatory protein 2) was identified using mouse steroidogenic factor 1 (SF1) as bait in a yeast two-hybrid screening of a human mammary gland cDNA expression library. PNRC2 is an unusual coactivator in that it is the smallest coactivator identified so far, with a molecular weight of 16 kDa, and interacts with nuclear receptors using a proline-rich sequence. In yeast two-hybrid assays PNRC2 interacted with orphan receptors SF1 and estrogen receptor-related receptor 
1 in a ligand-independent manner. PNRC2 was also found to interact with the ligand-binding domains of estrogen receptor, glucocorticoid receptor, progesterone receptor, thyroid receptor, retinoic acid receptor and retinoid X receptor in a ligand-dependent manner. A functional activation function 2 domain is required for nuclear receptors to interact with PNRC2. Using the yeast two-hybrid assay, the region amino acids 85–139 was found to be responsible for the interaction with nuclear receptors. This region contains an SH3 domain-binding motif (SEPPSPS) and an NR box-like sequence (LKTLL). A mutagenesis study has shown that the SH3 domain-binding motif is important for PNRC2 to interact with all the nuclear receptors tested. Our results reveal that PNRC2 has a structure and function similar to PNRC, a previously characterized coactivator. These two proteins represent a new type of nuclear receptor co-regulatory proteins.
* To whom correspondence should be addressed. Tel: +1 626 359 8111; Fax: +1 626 301 8186; Email: schen{at}coh.org
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]
|
|
|
|
 |
|
 D. Zhou, R. Shen, J. J. Ye, Y. Li, W. Tsark, D. Isbell, P. Tso, and S. Chen Nuclear Receptor Coactivator PNRC2 Regulates Energy Expenditure and Adiposity J. Biol. Chem., January 4, 2008; 283(1): 541 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yu, X. Wang, C.-F. Ng, S. Chen, and F. L. Chan ERR{gamma} Suppresses Cell Proliferation and Tumor Growth of Androgen-Sensitive and Androgen-Insensitive Prostate Cancer Cells and Its Implication as a Therapeutic Target for Prostate Cancer Cancer Res., May 15, 2007; 67(10): 4904 - 4914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. International Union of Pharmacology. LXVI. Orphan Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zhou, J. j. Ye, Y. Li, K. Lui, and S. Chen The molecular basis of the interaction between the proline-rich SH3-binding motif of PNRC and estrogen receptor alpha Nucleic Acids Res., November 6, 2006; 34(20): 5974 - 5986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Pan, L. Zhu, Y. Deng, and J. W. Pollard Microarray Analysis of Uterine Epithelial Gene Expression during the Implantation Window in the Mouse Endocrinology, October 1, 2006; 147(10): 4904 - 4916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Teuscher, R. W. Doerge, P. D. Fillmore, and E. P. Blankenhorn eae36, a Locus on Mouse Chromosome 4, Controls Susceptibility to Experimental Allergic Encephalomyelitis in Older Mice and Mice Immunized in the Winter Genetics, February 1, 2006; 172(2): 1147 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Cheung, S. Yu, K. B. Wong, L. W. Chan, F. M. M. Lai, X. Wang, M. Suetsugi, S. Chen, and F. L. Chan Expression and Functional Study of Estrogen Receptor-Related Receptors in Human Prostatic Cells and Tissues J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1830 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Albers, H. Kranz, I. Kober, C. Kaiser, M. Klink, J. Suckow, R. Kern, and M. Koegl Automated Yeast Two-hybrid Screening for Nuclear Receptor-interacting Proteins Mol. Cell. Proteomics, February 1, 2005; 4(2): 205 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chen, M. Cho, K. Karlsberg, D. Zhou, and Y.-C. Yuan Biochemical and Biological Characterization of a Novel Anti-aromatase Coumarin Derivative J. Biol. Chem., November 12, 2004; 279(46): 48071 - 48078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Borud, G. Mellgren, J. Lund, and M. Bakke Cloning and Characterization of a Novel Zinc Finger Protein that Modulates the Transcriptional Activity of Nuclear Receptors Mol. Endocrinol., November 1, 2003; 17(11): 2303 - 2319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Frasor, J. M. Danes, B. Komm, K. C. N. Chang, C. R. Lyttle, and B. S. Katzenellenbogen Profiling of Estrogen Up- and Down-Regulated Gene Expression in Human Breast Cancer Cells: Insights into Gene Networks and Pathways Underlying Estrogenic Control of Proliferation and Cell Phenotype Endocrinology, October 1, 2003; 144(10): 4562 - 4574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Oltra, I. Pfeifer, and R. Werner Ini, a Small Nuclear Protein that Enhances the Response of the Connexin43 Gene to Estrogen Endocrinology, July 1, 2003; 144(7): 3148 - 3158. [Abstract] [Full Text] [PDF]
|
|