デグロン、分解調節領域
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/12/21 12:12:39」(JST)
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A degron is a specific sequence of amino acids in a protein that directs the starting place of degradation. A degron sequence can occur at either the N or C-terminal region: these are called N-degrons or C-degrons respectively.
A temperature sensitive degron takes advantage of the N-end rule pathway, in which a destabilizing N-terminal residue dramatically decreases the in vivo half-life of a protein.[1] The degron is a fusion protein of ubiquitin, arginine, and DHFR. DHFR is dihydrofolate reductase, a mouse-derived enzyme that functions in the synthesis of thymine. It is also heat-labile - at a higher temperature of 37°C, becomes slightly unfolded and exposes an internal lysine, the site of poly-ubiquitination. Proteolysis is highly processive, and the protein is degraded by the proteasome. The degron can be fused to a gene to produce the corresponding temperature-sensitive protein. It is portable, and can be transferred on a plasmid.
A ligand controllable degron takes advantage of a mutant form of FKBP12 protein that can be controlled using a synthetic ligand.[2] Small molecule Shield1 binds specifically to the degron making it inactive. An inactive degron no longer promotes protein degradation. The degron is reactivated when the small molecule is removed by washing the cells and active protein degradation occurs through proteasome mediated proteolysis.[3]
References
- ^ Dohmen, R.J., P. Wu, and A. Varshavsky, Heat-inducible degron: a method for constructing temperature-sensitive mutants. Science, 1994. 263(5151): p. 1273-1276.
- ^ Schoeber JP, van de Graaf SF, Lee KP, Wittgen HG, Hoenderop JG, Bindels RJ,Conditional fast expression and function of multimeric TRPV5 channels using Shield-1.Am J Physiol Renal Physiol. 2009 Jan;296(1):F204-11
- ^ Chu BW, Banaszynski LA, Chen LC, Wandless TJ,Recent progress with FKBP-derived destabilizing domains,Bioorg Med Chem Lett. 2008 Nov 15;18(22):5941-4
See also
English Journal
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- Bhattacharyya S1, Renn JP1, Yu H2, Marko JF3, Matouschek A4.
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- The 26S proteasome is the molecular machine at the center of the ubiquitin proteasome system and is responsible for adjusting the concentrations of many cellular proteins. It is a drug target in several human diseases, and assays for the characterization of modulators of its activity are valuable. T
- PMID 27296635
- Autophagy in Saccharomyces cerevisiae requires the monomeric GTP-binding proteins, Arl1 and Ypt6.
- Yang S1, Rosenwald AG1.
- Autophagy.Autophagy.2016 Jul 27:1-17. [Epub ahead of print]
- Macroautophagy/autophagy is a cellular degradation process that sequesters organelles or proteins into a double-membrane structure called the phagophore; this transient compartment matures into an autophagosome, which then fuses with the lysosome or vacuole to allow hydrolysis of the cargo. Factors
- PMID 27462928
- Post-translational control of genetic circuits using Potyvirus proteases.
- Fernandez-Rodriguez J1, Voigt CA2.
- Nucleic acids research.Nucleic Acids Res.2016 Jul 27;44(13):6493-502. doi: 10.1093/nar/gkw537. Epub 2016 Jun 13.
- Genetic engineering projects often require control over when a protein is degraded. To this end, we use a fusion between a degron and an inactivating peptide that can be added to the N-terminus of a protein. When the corresponding protease is expressed, it cleaves the peptide and the protein is degr
- PMID 27298256
Japanese Journal
- Auxin-Mediated Transcriptional System with a Minimal Set of Components Is Critical for Morphogenesis through the Life Cycle in Marchantia polymorpha.
- 1P034 1YA0915 二つのプロテアソーム分解シグナルの配置解析(蛋白質-構造機能相関,日本生物物理学会若手奨励賞選考会,若手招待講演,第48回日本生物物理学会年会)
- Determination of a chloroplast degron in the regulatory domain of chlorophyllide a oxygenase
Related Links
- Shown here in green is IkBa, the Inhibitor of NF-κB and regulator of the immune system. The red region highlights a Ubiquitin-Independent degron A degron is a portion of a protein that is important in regulation of protein degradation ...
- Nature Methods is a science methodology journal publishing laboratory techniques and methods papers in the life sciences and areas of chemistry relevant to the life sciences. ... GFP fused to the aid degron is degraded in budding ...
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