Takara iDimerize Inducible Homodimer System \Each

The iDimerize Inducible Homodimer System lets you control the homodimerization of a protein of interest in live cells via a membrane permeant compound. The system includes the iDimerize Inducible Homodimer Vector Set 1, which contains two mammalian expression vectors encoding fusion tags that can be easily added to your protein of interest. The activity and localization of the resulting chimeric protein can be controlled by the addition of a small molecule to the cell medium. The system also includes the membrane-permeant compound, B/B Homodimerizer, required for homodimerization, and two linear selection markers for hygromycin and puromycin resistance.

How does iDimerize technology work? A chemical inducer of dimerization, or “dimerizer”, is a cell-permeant organic small molecule with two separate motifs that each bind with high affinity to a specific protein module (Dmr domain) fused onto the protein(s) of interest.Addition of the dimerizer brings the chimeric protein subunits into very close proximity to each other, mimicking the activation of the cellular event that dimerization of interest controls. B/B Homodimerizer induces self-association of two copies of the same protein whereas A/C Heterodimerizer induces association of two different proteins. Conversely, a reverse dimerizer ligand (D/D Solubilizer) will bind to and dissociate a protein that aggregates in its absence.

Signal transduction example 2.Inducible mouse model for prostate cancer. iDimerize Inducible Homodimer technology was used to characterize the role of different FGF receptor subtypes (FGFR1andFGFR2) in prostate cancer. Transgenic mice (which express conditionally active alleles ofFGFR1orFGFR2in prostate tissue) were treated with B/B Homodimerizer and monitored for prostate cancer.FGFR1, but notFGFR2, was found to play a role in prostate cancer development [Freeman, K. W.,et Al. (2003)Cancer Res.63(23):8256–8563].

Exploiting fas-mediated apoptosis to induce programmed cell death.Fas-mediated apoptosis is triggered by trimerization of the fas receptor (FasR) via its interaction with the fas ligand (FasL) on an adjacent cell (left). This FasR trimerization event activates the caspase 8 pathway. In the MaFIA mouse model, the fas death domain is fused to two repeats of a dimerization domain and expressed from a myeloid-specific promoter. Apoptosis of macrophage cells in this mouse is induced by treatment with B/B Homodimerizer (AP20187) (right).