This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mahajan, M. A.
Right arrow Articles by Samuels, H. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mahajan, M. A.
Right arrow Articles by Samuels, H. H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2002, p. 6883-6894, Vol. 22, No. 19
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.19.6883-6894.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

NRC-Interacting Factor 1 Is a Novel Cotransducer That Interacts with and Regulates the Activity of the Nuclear Hormone Receptor Coactivator NRC

Muktar A. Mahajan, Audrey Murray, and Herbert H. Samuels*

Departments of Pharmacology and Medicine, New York University School of Medicine, New York, New York 10016

Received 4 April 2002/ Returned for modification 10 May 2002/ Accepted 3 July 2002

We previously reported the cloning and characterization of a novel nuclear hormone receptor transcriptional coactivator, which we refer to as NRC. NRC is a 2,063-amino-acid nuclear protein which contains a potent N-terminal activation domain and several C-terminal modules which interact with CBP and ligand-bound nuclear hormone receptors as well as c-Fos and c-Jun. In this study we sought to clone and identify novel factors that interact with NRC to modulate its transcriptional activity. Here we describe the cloning and characterization of a novel protein we refer to as NIF-1 (NRC-interacting factor 1). NIF-1 was cloned from rat pituitary and human cell lines and was found to interact in vivo and in vitro with NRC. NIF-1 is a 1,342-amino-acid nuclear protein containing a number of conserved domains, including six Cys-2/His-2 zinc fingers, an N-terminal stretch of acidic amino acids, and a C-terminal leucine zipper-like motif. Zinc fingers 1 to 3 are potential DNA-binding BED finger domains recently proposed to play a role in altering local chromatin architecture. We mapped the interaction domains of NRC and NIF-1. Although NIF-1 does not directly interact with nuclear receptors, it markedly enhances ligand-dependent transcriptional activation by nuclear hormone receptors in vivo as well as activation by c-Fos and c-Jun. These results, and the finding that NIF-1 interacts with NRC in vivo, suggest that NIF-1 functions to regulate transcriptional activation through NRC. We suggest that NIF-1, and factors which associate with coactivators but not receptors, be referred to as cotransducers, which act in vivo either as part of a coactivator complex or downstream of a coactivator complex to modulate transcriptional activity. Our findings suggest that NIF-1 may be a functional component of an NRC complex and acts as a regulator or cotransducer of NRC function.

* Corresponding author. Mailing address: Departments of Pharmacology and Medicine, New York University School of Medicine, 550 First Ave., New York, NY 10016. Phone: (212) 263-6279. Fax: (212) 263-7701. E-mail: herbert.samuels{at}med.nyu.edu.

Molecular and Cellular Biology, October 2002, p. 6883-6894, Vol. 22, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.19.6883-6894.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Saghizadeh, M., Akhmedov, N. B., Yamashita, C. K., Gribanova, Y., Theendakara, V., Mendoza, E., Nelson, S. F., Ljubimov, A. V., Farber, D. B. (2009). ZBED4, a BED-Type Zinc-Finger Protein in the Cones of the Human Retina. IOVS 50: 3580-3588 [Abstract] [Full Text]  
  • Garapaty, S., Xu, C.-F., Trojer, P., Mahajan, M. A., Neubert, T. A., Samuels, H. H. (2009). Identification and Characterization of a Novel Nuclear Protein Complex Involved in Nuclear Hormone Receptor-mediated Gene Regulation. J. Biol. Chem. 284: 7542-7552 [Abstract] [Full Text]  
  • Garapaty, S., Mahajan, M. A., Samuels, H. H. (2008). Components of the CCR4-NOT Complex Function as Nuclear Hormone Receptor Coactivators via Association with the NRC-interacting Factor NIF-1. J. Biol. Chem. 283: 6806-6816 [Abstract] [Full Text]  
  • Das, S., Schapira, M., Tomic-Canic, M., Goyanka, R., Cardozo, T., Samuels, H. H. (2007). Farnesyl Pyrophosphate Is a Novel Transcriptional Activator for a Subset of Nuclear Hormone Receptors. Mol. Endocrinol. 21: 2672-2686 [Abstract] [Full Text]  
  • Mahajan, M. A., Murray, A., Levy, D., Samuels, H. H. (2007). Nuclear Receptor Coregulator (NRC): Mapping of the Dimerization Domain, Activation of p53 and STAT-2, and Identification of the Activation Domain AD2 Necessary for Nuclear Receptor Signaling. Mol. Endocrinol. 21: 1822-1834 [Abstract] [Full Text]  
  • Tian, H., Mahajan, M. A., Wong, C. T., Habeos, I., Samuels, H. H. (2006). The N-Terminal A/B Domain of the Thyroid Hormone Receptor-{beta}2 Isoform Influences Ligand-Dependent Recruitment of Coactivators to the Ligand-Binding Domain. Mol. Endocrinol. 20: 2036-2051 [Abstract] [Full Text]  
  • Mahajan, M. A., Samuels, H. H. (2005). Nuclear Hormone Receptor Coregulator: Role in Hormone Action, Metabolism, Growth, and Development. Endocr. Rev. 26: 583-597 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»