ITCH (D8Q6D) Rabbit mAb #12117
- WB
- IP
Supporting Data
| REACTIVITY | H M R |
| SENSITIVITY | Endogenous |
| MW (kDa) | 105 |
| Source/Isotype | Rabbit IgG |
Application Key:
- WB-Western Blotting
- IP-Immunoprecipitation
Species Cross-Reactivity Key:
- H-Human
- M-Mouse
- R-Rat
Product Information
Product Usage Information
| Application | Dilution |
|---|---|
| Western Blotting | 1:1000 |
| Immunoprecipitation | 1:200 |
Storage
Protocol
Specificity / Sensitivity
Species Reactivity:
Source / Purification
Background
Further characterizations revealed that Itch encoded a NEDD4-like E3-ubiquitin ligase capable of catalyzing Lys29, Lys48, and/or Lys63-linked ubiquitination of target proteins, leading to their degradation by the proteosome pathway (4-6). The distinct phenotypes of Itch mutant mice led to the identification of an important regulatory role for ITCH-mediated ubiquitination in inflammatory signaling pathways. For example, ITCH-mediated ubiquitination of the transcription factor JunB was shown to play a direct inhibitory role in regulating expression of the proinflammatory cytokine IL-4. ITCH-null T lymphocytes consequently exhibit increased production of IL-4, leading to biased differentiation of naive CD4+ cells towards the proinflammatory Th2 lineage (7). In accordance with the findings from mutant Itch mouse models, a genetic linkage study in humans identified loss-of-function mutations in ITCH as a direct cause of syndromic multisystem autoimmune disease (SMAD) (8).
Notably, targets of ITCH-mediated ubiquitination are not restricted to immune signaling pathways. For example, key mediators of the Hedgehog (9,10), Wnt/β-catenin (11), Hippo (12), and Notch signaling pathways (13,14) have been identified as important targets of ITCH-mediated ubiquitination (2).
- Matesic, L.E. et al. (2008) Curr Top Microbiol Immunol 321, 185-200.
- Melino, G. et al. (2008) Cell Death Differ 15, 1103-12.
- Perry, W.L. et al. (1998) Nat Genet 18, 143-6.
- Chastagner, P. et al. (2006) EMBO Rep 7, 1147-53.
- Lee, T.L. et al. (2008) Biochem Biophys Res Commun 375, 326-30.
- Ahmed, N. et al. (2011) Nat Immunol 12, 1176-83.
- Fang, D. et al. (2002) Nat Immunol 3, 281-7.
- Lohr, N.J. et al. (2010) Am J Hum Genet 86, 447-53.
- Di Marcotullio, L. et al. (2006) Nat Cell Biol 8, 1415-23.
- Di Marcotullio, L. et al. (2011) Oncogene 30, 65-76.
- Wei, W. et al. (2012) Mol Cell Biol 32, 3903-12.
- Salah, Z. et al. (2011) Cancer Res 71, 2010-20.
- Qiu, L. et al. (2000) J Biol Chem 275, 35734-7.
- McGill, M.A. and McGlade, C.J. (2003) J Biol Chem 278, 23196-203.
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