&amp;beta;-catenin takes a HIT

Huber, Otmar; Weiske, Jörg

doi:10.4161/cc.7.10.5926

Cited by 27 publications

(19 citation statements)

References 72 publications

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“…More recently, down regulation of Fhit protein expression has been associated with DNA fragility and damage [46] , and also a close link between the location of the fragile gene with many of the known breakpoints in cancer specific chromosomal translocations [47] . Fhit staining intensity in our patients had a strong association with smoking and non-vegetarian dietary intakes, thereby re-confirming the previous hypothesis of epigenetic factors in deletions and dysregulation in Fhit gene, as in lung cancer development [16][17][18][19]21,22,24,48] . Many of our carcinoma cases were negative for Fhit protein although expression for the protein was retained by a couple of cases which could be the result of a dysregulated gene that have been observed in other tumors, including lungs and breast [20,21,24,33,43,48] .…”

Section: Discussionsupporting

confidence: 89%

“…Similarly to our observations, gradual reductions in the intensity of Fhit protein had been reported by other groups in colon cancer and its early precursor lesions, and also in other pre-neoplastic lesions in breast, pan- T1 T2 T3 T4 N0 N1 N2 M0 M1 Total Negative 9 3 12 12 12 Weak 3 14 1 10 8 18 18 Moderate 16 2 8 7 3 15 3 18 Strong 24 3 27 0 27 27 Total 3 63 9 57 15 3 72 3 75 creas, cervix, lung and esophagus [15][16][17][18]20,21,[25][26][27][28][29][30][31]33,43,44] . Functional loss of the tumor suppressor protein Fhit, like p53, is believed to result in loss of inhibitory function in cell proliferation due to release phenomena in many downstream proteins acting on cell proliferations [16][17][18][19]45] . More recently, down regulation of Fhit protein expression has been associated with DNA fragility and damage [46] , and also a close link between the location of the fragile gene with many of the known breakpoints in cancer specific chromosomal translocations [47] .…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal expressions of Fhit gene has been identified in various human cancers and cancer cell lines, including gastrointestinal cancers. Genetic and epigenetic alterations result in homozygous genomic deletions in Fhit gene and down regulation of the Fhit protein in various carcinomas [16][17][18][19] . In lung cancer, aberrant Fhit protein expression and inactivation of the Fhit gene has been attributed to smoking [18,20,21] .…”

Section: Introductionmentioning

confidence: 99%

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Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma

Vaiphei

Rangan²,

Singh³

2012

WJGO

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AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67.METHODS: ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson's χ 2 test and γ test for the ordinal data. P value < 0.05 was considered as significant. RESULTS:Age range was 40 to 86 years in males (mean = 43.36) and 45 to 70 years in females (mean = 56). HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32%) had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression: (1) HACF -40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2) DACF -strong in 25%, moderate in 37.5% and weak in 37.5%; and (3) carcinoma -negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05). Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036). Vegetarian diet intake and nonsmokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05). Fhit protein had an inverse association with Ki67 expression. CONCLUSION:Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma

Vaiphei

Rangan²,

Singh³

2012

WJGO

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“…b-catenin's oncogenic potential is well documented, and mutations resulting in its stabilization and nuclear accumulation have been observed in various carcinomas (Gavert and Ben-Ze'ev, 2007;Huang and He, 2008;Huber and Weiske, 2008;Jeanes et al, 2008;Jin et al, 2008). In contrast, plakoglobin has typically been associated with tumor/metastasis-suppressor activity, although the mechanism behind this activity is not understood (Simcha et al, 1996;Pantel et al, 1998;Parker et al, 1998;Winn et al, 2002;Reiger-Christ et al, 2005;Kanazawa et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

et al. 2010

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Plakoglobin (c-catenin) is a homolog of b-catenin with similar dual adhesive and signaling functions. The adhesive function of these proteins is mediated by their interactions with cadherins, whereas their signaling activity is regulated by association with various intracellular partners. In this respect, b-catenin has a well-defined oncogenic activity through its role in the Wnt signaling pathway, whereas plakoglobin acts as a tumor/metastasis suppressor through mechanisms that remain unclear. We previously expressed plakoglobin in SCC9 squamous carcinoma cells (SCC9-P) and observed a mesenchymalto-epidermoid transition. Comparison of the protein and RNA profiles of parental SCC9 cells and SCC9-P transfectants identified various differentially expressed proteins and transcripts, including the nonmetastatic protein 23 (Nm23). In this study, we show that Nm23-H1 mRNA and Nm23-H2 protein are increased after plakoglobin expression. Coimmunoprecipitation and confocal microscopy studies using SCC9-P and various epithelial cell lines with endogenous plakoglobin expression revealed that Nm23 interacts with plakoglobin, cadherins and a-catenin. Furthermore, Nm23-H2 is the primary isoform involved in these interactions, which occur prominently in the cytoskeleton-associated pool of cellular proteins. In addition, we show that plakoglobinNm23 interaction requires the N-terminal (a-catenin interacting) domain of plakoglobin. Our data suggest that by increasing the expression and stability of Nm23, plakoglobin has a role in regulating the metastasis suppressor activity of Nm23, which may further provide a potential mechanism for the tumor/metastasis suppressor function of plakoglobin itself.

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“…Animal HIT proteins such as Hint and Fhit are present in the nucleus, the cytosol, or mitochondria, hydrolyzing substrates such as AMP-NH 2 , AMP-Lys, and diadenosinpolyphosphates (Ap n A; n = 3 or 4; Huber and Weiske, 2008). Although the direct biological consequences of their catalytic activities are unclear, HIT proteins have been found to play crucial roles in tumorigenesis by regulating the function of transcription complexes and possibly other unidentified enzymes (Huber and Weiske, 2008).…”

Section: A New Family Of Nucleotide-binding Proteinsmentioning

confidence: 99%

In-Depth Proteome Analysis of Arabidopsis Leaf Peroxisomes Combined with in Vivo Subcellular Targeting Verification Indicates Novel Metabolic and Regulatory Functions of Peroxisomes

et al. 2009

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Peroxisomes are metabolically diverse organelles with essential roles in plant development. The major protein constituents of plant peroxisomes are well characterized, whereas only a few low-abundance and regulatory proteins have been reported to date. We performed an in-depth proteome analysis of Arabidopsis (Arabidopsis thaliana) leaf peroxisomes using onedimensional gel electrophoresis followed by liquid chromatography and tandem mass spectrometry. We detected 65 established plant peroxisomal proteins, 30 proteins whose association with Arabidopsis peroxisomes had been previously demonstrated only by proteomic data, and 55 putative novel proteins of peroxisomes. We subsequently tested the subcellular targeting of yellow fluorescent protein fusions for selected proteins and confirmed the peroxisomal localization for 12 proteins containing predicted peroxisome targeting signals type 1 or 2 (PTS1/2), three proteins carrying PTS-related peptides, and four proteins that lack conventional targeting signals. We thereby established the tripeptides SLM. and SKV. (where . indicates the stop codon) as new PTS1s and the nonapeptide RVx 5 HF as a putative new PTS2. The 19 peroxisomal proteins conclusively identified from this study potentially carry out novel metabolic and regulatory functions of peroxisomes. Thus, this study represents an important step toward defining the complete plant peroxisomal proteome.Surrounded by single membranes, peroxisomes are small, ubiquitous eukaryotic organelles mediating a wide range of oxidative metabolic activities that vary by the species, cell type, and environmental conditions in which the organism lives (Beevers, 1979;Van den Bosch et al., 1992). Plant peroxisomes are essential to physiological processes such as lipid metabolism, photorespiration, and plant hormone biosynthesis and metabolism (Olsen and Harada,

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β-catenin takes a HIT

Cited by 27 publications

References 72 publications

Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma

Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

In-Depth Proteome Analysis of Arabidopsis Leaf Peroxisomes Combined with in Vivo Subcellular Targeting Verification Indicates Novel Metabolic and Regulatory Functions of Peroxisomes

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