NRC-Interacting Factor 1 Is a Novel Cotransducer That Interacts with and Regulates the Activity of the Nuclear Hormone Receptor Coactivator NRC
| Autor: | Audrey Murray, Herbert H. Samuels, Muktar A. Mahajan |
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| Rok vydání: | 2002 |
| Předmět: |
Transcription
Genetic Amino Acid Motifs Molecular Sequence Data Nuclear Receptor Coactivators Biology Cell Line Two-Hybrid System Techniques Coactivator Animals Humans Amino Acid Sequence Cloning Molecular Nuclear protein Molecular Biology Transcription factor Conserved Sequence health care economics and organizations Transcriptional Regulation Zinc finger Leucine Zippers Sequence Homology Amino Acid Intracellular Signaling Peptides and Proteins Nuclear Proteins Zinc Fingers Cell Biology biochemical phenomena metabolism and nutrition Protein Structure Tertiary Rats DNA-Binding Proteins Nuclear receptor coactivator 1 Gene Expression Regulation Nuclear receptor Biochemistry Nuclear receptor coactivator 3 Nuclear receptor coactivator 2 Carrier Proteins Protein Binding Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 22:6883-6894 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.22.19.6883-6894.2002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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