Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains.

Date publication

août 1997

Journal

Biochemical and biophysical research communications

Auteurs

Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre , Dr METZGER Daniel

Tous les auteurs :
Feil R, Wagner J, Metzger D, Chambon P

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/9299439

Résumé

Ligand-dependent chimeric Cre recombinases are powerful tools to induce specific DNA rearrangements in cultured cells and in mice. We report here the construction and characterization of a series of chimeric recombinases, each consisting of Cre fused to a mutated human oestrogen receptor (ER) ligand-binding domain (LBD). Two new ligand-dependent recombinases which contain either the G400V/M543A/L544A or the G400V/L539A/L540A triple mutation of the human ER LBD are efficiently induced by the synthetic ER antagonists 4-hydroxytamoxifen (OHT) and ICI 182,780 (ICI), respectively, but are insensitive to 17 beta-oestradiol (E2). Both chimeric recombinases should be useful for efficient spatio-temporally controlled site-directed somatic mutagenesis.

Mots clés

Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Enzyme Induction, drug effects, Estradiol, analogs & derivatives, Estrogen Antagonists, pharmacology, Humans, Integrases, biosynthesis, Kinetics, Mice, Molecular Sequence Data, Mutagenesis, Insertional, Mutagenesis, Site-Directed, Oligodeoxyribonucleotides, Point Mutation, Receptors, Estrogen, biosynthesis, Recombinant Fusion Proteins, biosynthesis, Tamoxifen, analogs & derivatives, Teratoma, Tumor Cells, Cultured, Viral Proteins

Référence

Biochem. Biophys. Res. Commun.. 1997 Aug;237(3):752-7