Nuclear hormone receptor coregulator: role in hormone action, metabolism, growth, and development
| Autor: | Herbert H. Samuels, Muktar A. Mahajan |
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| Rok vydání: | 2004 |
| Předmět: |
Transcription
Genetic Protein Conformation Endocrinology Diabetes and Metabolism Nuclear Receptor Coactivators Regulator Gene Expression Apoptosis Growth Biology Mice Endocrinology Transcription (biology) Neoplasms Gene expression Animals Humans Protein Isoforms Cloning Molecular Gene Transcription factor health care economics and organizations Mice Knockout Wound Healing Reproduction Intracellular Signaling Peptides and Proteins Phenotype Hormones Cell biology Biochemistry Nuclear receptor Dimerization Hormone Transcription Factors |
| Zdroj: | Endocrine reviews. 26(4) |
| ISSN: | 0163-769X |
| Popis: | Nuclearhormonereceptorcoregulator(NRC)(alsoreferredto as activating signal cointegrator-2, thyroid hormone receptor-binding protein, peroxisome proliferator activating receptor-interacting protein, and 250-kDa receptor associated protein)belongstoagrowingclassofnuclearcofactorswidely known as coregulators or coactivators that are necessary for transcriptional activation of target genes. The NRC gene is also amplified and overexpressed in breast, colon, and lung cancers. NRC is a 2063-amino acid protein that harbors a potent N-terminal activation domain (AD1) and a second more centrally located activation domain (AD2) that is rich in Glu and Pro. Near AD2 is a receptor-interacting domain containing an LxxLL motif (LxxLL-1), which interacts with a wide variety of ligand-bound nuclear hormone receptors with high affinity. A second LxxLL motif (LxxLL-2) located in the Cterminal region of NRC is more restricted in its nuclear hormone receptor specificity. The intrinsic activation potential ofNRCisregulatedbyaC-terminalserine,threonine,leucineregulatory domain. The potential role of NRC as a cointegrator is suggested by its ability to enhance transcriptional activation of a wide variety of transcription factors and from its in vivo association with a number of known transcriptional regulators including CBP/p300. Recent studies in mice indicate that deletion of both NRC alleles leads to embryonic lethality resulting from general growth retardation coupled with developmental defects in the heart, liver, brain, and placenta. NRC / mouse embryo fibroblasts spontaneously undergo apoptosis, indicating the importance of NRC as a prosurvival and antiapoptotic gene. Studies with 129S6 NRC / mice indicate that NRC is a pleiotropic regulator that is involved in growth, development, reproduction, metabolism, and wound healing. (Endocrine Reviews 26: 583–597, 2005) |
| Databáze: | OpenAIRE |
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