Disease relevance of CTNNBIP1

• Real-time RT-PCR showed markedly reduced ICAT transcript levels (<or=20% relative to normal skin and benign melanocytic nevi) in 28/36 malignant melanomas (78%), including 13/14 tumors with LOH on 1p36 [1].
• Mutation and expression of the beta-catenin-interacting protein ICAT in human colorectal tumors [2].
• Cases exhibiting ICAT overexpression showed a significantly higher incidence of well-differentiated adenocarcinoma and positive lymphatic permeation [2].
• In the latter case, the ICAT method produced significant new information on changes that occur in protein expression levels in a patient suffering from cystic fibrosis [3].
• Using ICAT/MS/MS we profiled the nuclear, cytosolic, and microsomal fractions obtained from IGOV-1 (cisplatin-sensitive) and IGOV-1/CP (cisplatin-resistant) ovarian cancer cell lines [4].

High impact information on CTNNBIP1

• Taken together, these data demonstrate that LZTS2 is a beta-catenin-interacting protein that can modulate beta-catenin signaling and localization [5].
• In a yeast two-hybrid screen, we identified the four and a half of LIM-only protein 2 (FHL2) as a novel beta-catenin-interacting protein [6].
• Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation [7].
• Overexpression of ICAT highlights a rolefor catenin-mediated canonical Wnt signalling in early T cell development [8].
• None of the tumors had lost both copies of the ICAT gene, but 1 melanoma metastasis carried a somatic point mutation altering the translation start codon of ICAT [1].

Biological context of CTNNBIP1

• RESULTS: The ICAT gene was mapped to chromosome 1p36.1-p36.2, which is implicated in the pathogenesis of various types of cancers [2].

Anatomical context of CTNNBIP1

• MDCK cells overexpressing ICAT do, however, exhibit enhanced cell scattering on hepatocyte growth factor treatment, suggesting a possible role in the regulation of dynamic rather than steady-state cell-cell adhesions [9].
• However, ICAT protein levels are not altered by activation or inhibition of Wnt signaling in cultured cells, suggesting that ICAT expression is not a direct target of the Wnt/beta-catenin pathway [9].
• Tachykinins can depolarize neurons by two distinct mechanisms: 1) they reduce a resting K+ current in many neurons or 2) in parasympathetic and vagal primary sensory neurons, they activate a nonspecific cation current (Icat) [10].

Associations of CTNNBIP1 with chemical compounds

• Here, the LZIC gene, a novel gene encoding a 190-amino-acid polypeptide with leucine zipper domain and ICAT homologous domain, was cloned and characterized [11].
• Three derivatizing agents were examined, the do and d3 forms of N-acetoxysuccinimide, the do and d4 forms of succinic anhydride, and the do and d8 forms of the commercial ICAT reagent Peptide mixtures from control and experimental samples were derivatized individually, mixed, subjected to reversed-phase chromatography, and analyzed by ESI-MS [12].
• These light ICAT reagents give smooth mass spectral signals in tandem mass spectrometry (MS/MS) analyses of some commercially available cysteine-containing peptides [13].
• Since the biotin moiety can be readily cleaved off the reagent after mass tagging, undesired residual fragmentation patterns caused by biotin of derived peptides, as normally observed using biotin-containing ICAT reagents, are effectively eliminated [13].
• Icat reached its peak value in approximately 3 min (195 +/- 120.0 s, mean +/- SE, n = 20), had a peak density of 11.3 +/- 3.48 pA/pF (n = 24), and was blocked by an NK2R-specific antagonist (SR48968, 100 nM) [10].

Other interactions of CTNNBIP1

• Molecular cloning and characterization of LZIC, a novel gene encoding ICAT homologous protein with leucine zipper domain [11].
• These findings confirm ICAT's primary role in beta-catenin signaling inhibition and further suggest that ICAT may have consequences for cadherin-based adhesive function in certain circumstances, implying a broader role than previously described [9].
• In support of this, over-expression of N-cadherin, ICAT or dnTCF-4 in isolated human VSMCs significantly lowered levels of cyclin D1 mRNA and protein levels [14].
• N-cadherin, ICAT or dnTCF-4 over-expression significantly reduced proliferation of isolated human VSMCs by approximately 55%, 80%, and 45% respectively [14].

Analytical, diagnostic and therapeutic context of CTNNBIP1

• By direct retroviral gene targeting of CD4(-)8(-) and CD4(+)8(+) precursors, we show that ICAT overexpression inhibits the CD4(-)8(-)-to-CD4(+)8(+) transition, but not the CD4(+)8(+)-to-CD4(+)8(-) or -CD4(-)8(+) transition [8].
• Recently, several methodologies using isotope labeling of proteins for quantitative proteomic studies have been introduced (e.g. using ICAT reagents or growing cells in isotopically enriched nutrients) [15].
• Cleavable ICAT-labeled tryptic peptides were separated from nonlabeled peptides by avidin affinity chromatography [3].
• These tools include 2-DE, 2D-DIGE, ICAT, protein arrays, MudPIT and mass spectrometries including SELDI-TOF [16].

References