#Q53G59
59349
Product Information
Product Usage Information
CST recommends transfection with 100 nM SignalSilence® KLHL12 siRNA II 48 to 72 hours prior to cell lysis. For transfection procedure, follow protocol provided by the transfection reagent manufacturer. Please feel free to contact CST with any questions on use. Each vial contains the equivalent of 100 transfections, which corresponds to a final siRNA concentration of 100 nM per transfection in a 24-well plate with a total volume of 300 μl per well.
Storage
Specificity / Sensitivity
Species Reactivity:
Human
Species predicted to react based on 100% sequence homology
The antigen sequence used to produce this antibody shares
100% sequence homology with the species listed here, but
reactivity has not been tested or confirmed to work by CST.
Use of this product with these species is not covered under
our
Product Performance Guarantee.
Monkey
Product Description
Background
Cullins are proteins that function as molecular scaffolds for modular ubiquitin ligases typified by the SCF (Skp1-CUL1-F-box) complex (1-3). The substrate selectivity of these E3 ligases is dictated by a specificity module that binds cullins. In the SCF complex, this module is composed of Skp1, which binds directly to CUL1, and a member of the F-box family of proteins such as Skp2 (1-4). CUL3 has been shown to be required for embryonic development in mammals and Caenorhabditis elegans (5-7) but until recently, its substrate specificity adaptor had yet to be elucidated. It is now recognized that substrate adaptors for CUL3-based ubiquitin ligase complexes contain a conserved BTB/POZ (Pox virus and Zinc finger) domain. This domain, which was initially identified in the Drosophila transcriptional repressors broad complex, tramtrack, and bric-a-brac is present in more than 190 human proteins. BTB proteins contain a variety of putative protein-protein interaction domains, including MATH domains, zinc finger repeats, and kelch repeats (8).
There are several lines of evidence suggesting that Kelch-like 12 protein (KLHL12) is a substrate-specific adaptor for the CUL3-based ubiquitin ligase complex. Analysis of the amino acid sequence of KLHL12 reveals an amino-terminal BTB motif, a central linker region, and a carboxy-terminal kelch domain composed of kelch repeats. Furthermore, KLHL12 has been shown to negatively regulate Wnt signaling by binding Disheveled and targeting it for ubiquitin-dependent proteasomal degradation (9). More recently, KLHL12 was shown to drive the assembly of large COPII vesicles by promoting the monoubiquitination of the COPII component Sec31. As a result, CUL3-KLHL12-dependent ubiquitination is essential for collagen export, a step that is required for integrin-dependent mouse embryonic stem cell division (10).
- Zheng, N. et al. (2002) Nature 416, 703-9.
- Skowyra, D. et al. (1997) Cell 91, 209-19.
- Feldman, R.M. et al. (1997) Cell 91, 221-30.
- Bai, C. et al. (1996) Cell 86, 263-74.
- Singer, J.D. et al. (1999) Genes Dev 13, 2375-87.
- Winston, J.T. et al. (1999) Genes Dev 13, 2751-7.
- Kurz, T. et al. (2002) Science 295, 1294-8.
- Collins, T. et al. (2001) Mol Cell Biol 21, 3609-15.
- Angers, S. et al. (2006) Nat Cell Biol 8, 348-57.
- Jin, L. et al. (2012) Nature 482, 495-500.
Species Reactivity
Species reactivity is determined by testing in at least one approved application (e.g., western blot).
Cross-Reactivity Key
H: human M: mouse R: rat Hm: hamster Mk: monkey Vir: virus Mi: mink C: chicken Dm: D. melanogaster X: Xenopus Z: zebrafish B: bovine Dg: dog Pg: pig Sc: S. cerevisiae Ce: C. elegans Hr: horse GP: Guinea Pig Rab: rabbit All: all species expected
Trademarks and Patents
Limited Uses
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