Genomic Structure and DNA Binding Properties of the Human Zinc Finger Transcriptional Repressor AP-2rep (KLF12)

Roth, Christina; Schuierer, Marion; Günther, Kalle; Buettner, Reinhard

doi:10.1006/geno.1999.6084

Cited by 47 publications

(49 citation statements)

References 24 publications

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“…None of the genes in our signature set have been previously associated with lymph node metastasis in HNSCC, although different experimental methods have implicated some in squamous cell cancer (TDRD1 (Loriot et al, 2003), transglutaminase 3 (Chen et al, 2000), ERBB4 (Bei et al, 2001), keratin 13 (Depondt et al, 1999)) and correlated others with aggressiveness and invasiveness of a diverse group of primary tumors (ERBB4 and keratin 13, OSCC (Depondt et al, 1999;Bei et al, 2001); KLF12, melanoma (Karjalainen et al, 1998;Roth et al, 2000); ATP6V1C1, pancreatic (Ohta et al, 1996); KCNJ5, breast (Kennedy et al, 1999;Stringer et al, 2001)). Unexpectedly CXCR4, which has been previously correlated with metastasis in HNSCC as well as other tumor types, did not emerge in our list of differentially expressed genes (Uchida et al, 2003;Delilbasi et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

“…Overexpression of its binding partner, GIRK1, was found to be correlated with lymph node metastasis in breast carcinoma (Stringer et al, 2001). Downregulation of the transcription factor AP-2 is associated with metastasis in melanoma, and our signature gene set includes upregulated KLF12, an AP-2 repressor gene (Karjalainen et al, 1998;Roth et al, 2000). Vacuolar ATP synthase subunit C, overexpressed in our N þ patients, has been correlated with invasiveness of pancreatic tumors (Ohta et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

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Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

et al. 2004

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Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was built using a support vector machine, and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

et al. 2004

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“…We provide here the first evidence that APC is a direct binding partner of AP-2␣, but several other AP-2␣-interacting proteins have been identified, including retinoblastoma protein (16,31), Myc (17,19), SV-40 large T antigen (32), human T-cell leukemia virus type 1 (33), PC4 (34), poly(ADP-ribose) polymerase (18), KLF9, and KLF12 (35,36). Many of these AP-2␣-binding proteins are well established regulators of gene expression.…”

Section: Discussionmentioning

confidence: 97%

Activator Protein 2α Associates with Adenomatous Polyposis Coli/β-Catenin and Inhibits β-Catenin/T-cell Factor Transcriptional Activity in Colorectal Cancer Cells

Dashwood

2004

Journal of Biological Chemistry

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In most human colorectal cancers, mutations in the adenomatous polyposis coli gene (APC) or CTNNB1 constitutively activate the ␤-catenin/T-cell factor (TCF)/ lymphoid enhancer factor (LEF) signaling pathway. Here, we show that the transcription factor activator protein (AP)-2␣ inhibited a ␤-catenin/TCF-responsive reporter in human embryonic kidney 293 cells and in two human colorectal cancer lines, despite the fact that ␤-catenin and TCF-4 protein levels were unchanged in the nucleus. Co-immunoprecipitation studies revealed that AP-2␣ formed a complex with APC and ␤-catenin and that AP-2␣ disrupted ␤-catenin/TCF-4 interactions in the nucleus. Thus, AP-2␣⅐APC⅐␤-catenin complex formation appears to suppress ␤-catenin transactivation by shifting the pool of nuclear ␤-catenin toward an inactive form, having reduced binding to TCF/LEF transcription factors. Glutathione S-transferase pull-down assays showed that AP-2␣ physically associated with APC rather than with ␤-catenin, and the AP-2␣ binding site was identified in the N terminus of APC, involving both the heptad and armadillo repeat domains, whereas the APC binding site in AP-2␣ was in the basic region of the C-terminal DNA binding domain. These findings provide the first evidence for a specific interaction between the tumor suppressor protein APC and the transcription factor AP-2␣, and they suggest a link between the Wnt signaling pathway and various other pathways of development and differentiation associated with AP-2␣.

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“…Notably, we also showed that Grhl2 regulates expression of Klf12, a Kruppel-like transcription factor that directly represses expression of the helix-loop-helix transcription factor AP-2␣ (56). AP-2␣, in turn, directly regulates expression of Cdh1 (57).…”

Section: Discussionmentioning

confidence: 99%

The Transcription Factors Grainyhead-like 2 and NK2-Homeobox 1 Form a Regulatory Loop That Coordinates Lung Epithelial Cell Morphogenesis and Differentiation

Varma

Cao

Tagne

et al. 2012

Journal of Biological Chemistry

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Background: Grhl2 regulates cell-junction gene transcription in several epithelia but has not been fully characterized in lungs. Results: In lung epithelial cells GRHL2 regulates cell-cell interaction genes, collective cell migration, and Nkx2-1 transcription. Conversely, NKX2-1 regulates transcription of Grhl2. Conclusion: A Grhl2-and Nkx2-1-positive transcriptional loop coordinates morphogenesis and differentiation of lung epithelial cells. Significance: This regulatory loop reinforces normal lung epithelial cell identity.

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Genomic Structure and DNA Binding Properties of the Human Zinc Finger Transcriptional Repressor AP-2rep (KLF12)

Cited by 47 publications

References 24 publications

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

Activator Protein 2α Associates with Adenomatous Polyposis Coli/β-Catenin and Inhibits β-Catenin/T-cell Factor Transcriptional Activity in Colorectal Cancer Cells

The Transcription Factors Grainyhead-like 2 and NK2-Homeobox 1 Form a Regulatory Loop That Coordinates Lung Epithelial Cell Morphogenesis and Differentiation

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