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Product Information
Product Usage Information
CST recommends transfection with 100 nM SignalSilence® TAB3 siRNA I 48 to 72 hours prior to cell lysis. For transfection procedure, follow the 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
Product Description
Background
TAK1 is a mitogen-activated protein kinase kinase kinase activated by TGF-β and various pro-inflammatory signals (1,2). In vivo, TAK1 activation requires its association with TAK1 binding protein 1 (TAB1), which triggers TAK1 autophosphorylation at Thr184 and Thr187 (3,4). The TAB2 adaptor protein links TAK1 with TRAF6 to mediate TAK1 activation following IL-1 stimulation (5). Once activated, TAK1 phosphorylates the MAPK kinases MKK4 and MKK3/6, which activate JNK and p38 MAPK, respectively. TAK1 and TRAF6 also activate the NF-κB pathway by phosphorylating the NF-κB inducing kinase (NIK) to trigger subsequent activation of IKK (2,6). In addition to TAK1, TAB1 interacts with and activates p38α MAPK (7). Targeted disruption of the TAB1 gene in mice causes a drastic reduction in TAK1 activity and leads to embryonic lethality (8).
TAK1-binding protein 3 (TAB3) is an additional binding partner for TAK1 and appears to be functionally redundant to TAB2 protein (9,10). The carboxy-terminal zinc finger domains in TAB2 and TAB3 bind to lysine 63-linked polyubiquitin chains within target proteins, including TRAF6, IKKγ, and RIP, which results in activation of IKK (11). Research studies also indicate that TAB2 and TAB3 proteins negatively regulate autophagy through interaction with beclin-1 (12,13).
- Yamaguchi, K. et al. (1995) Science 270, 2008-11.
- Ninomiya-Tsuji, J. et al. (1999) Nature 398, 252-6.
- Shibuya, H. et al. (1996) Science 272, 1179-82.
- Sakurai, H. et al. (2000) FEBS Lett 474, 141-5.
- Takaesu, G. et al. (2000) Mol Cell 5, 649-58.
- Wang, C. et al. (2001) Nature 412, 346-51.
- Ge, B. et al. (2002) Science 295, 1291-4.
- Komatsu, Y. et al. (2002) Mech Dev 119, 239-49.
- Cheung, P.C. et al. (2004) Biochem J 378, 27-34.
- Jin, G. et al. (2004) Proc Natl Acad Sci U S A 101, 2028-33.
- Kanayama, A. et al. (2004) Mol Cell 15, 535-48.
- Takaesu, G. et al. (2012) J Biochem 151, 157-66.
- Criollo, A. et al. (2011) EMBO J 30, 4908-20.
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
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Limited Uses
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