The Peptide Near the C Terminus Regulates Receptor CAR Nuclear Translocation Induced by Xenochemicals in Mouse Liver
Autor: | Tatsuya Sueyoshi, Igor Zelko, Masahiko Negishi, Rick Moore, Takeshi Kawamoto |
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Rok vydání: | 2001 |
Předmět: |
Recombinant Fusion Proteins
Green Fluorescent Proteins Molecular Sequence Data Cell Gene Expression Biological Transport Active Receptors Cytoplasmic and Nuclear Chromosomal translocation Peptide Gene delivery Biology Cell Line Xenobiotics Mice medicine Animals Humans Amino Acid Sequence Receptor Molecular Biology Constitutive Androstane Receptor Sequence Deletion Cell Nucleus chemistry.chemical_classification C-terminus Mutagenesis Cell Biology Molecular biology Rats Luminescent Proteins medicine.anatomical_structure Liver Nuclear receptor chemistry Phenobarbital Mutagenesis Site-Directed Transcription Factors |
Zdroj: | Molecular and Cellular Biology. 21:2838-2846 |
ISSN: | 1098-5549 6318-6322 |
DOI: | 10.1128/mcb.21.8.2838-2846.2001 |
Popis: | In response to phenobarbital (PB) and other PB-type inducers, the nuclear receptor CAR translocates to the mouse liver nucleus (T. Kawamoto et al., Mol. Cell. Biol. 19:6318-6322, 1999). To define the translocation mechanism, fluorescent protein-tagged human CAR (hCAR) was expressed in the mouse livers using the in situ DNA injection and gene delivery systems. As in the wild-type hCAR, the truncated receptor lacking the C-terminal 10 residues (i.e., AF2 domain) translocated to the nucleus, indicating that the PB-inducible translocation is AF2 independent. Deletion of the 30 C-terminal residues abolished the receptor translocation, and subsequent site-directed mutagenesis delineated the PB-inducible translocation activity of the receptor to the peptide L313GLL316AEL319. Ala mutations of Leu313, Leu316, or Leu319 abrogated the translocation of CAR in the livers, while those of Leu312 or Leu315 did not affect the nuclear translocation. The leucine-rich peptide dictates the nuclear translocation of hCAR in response to various PB-type inducers and appears to be conserved in the mouse and rat receptors. |
Databáze: | OpenAIRE |
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