Molecular Cloning and Characterization of a Transcription Regulator with Homology to GC-binding Factor

Reed, Andre L.; Yamazaki, Hitoshi; Kaufman, Joshua D.; Rubinstein, Yaffa; Murphy, Barbara A.; Johnson, Ann L.

doi:10.1074/jbc.273.34.21594

Cited by 52 publications

(46 citation statements)

References 38 publications

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“…The first, homologous to the ␤3b domain, is a cDNA (U69609 and AJ223075) encoding a transcription factor, GCF2 (32,33). Although transcribed from an independent gene (see mapping data below), this cDNA is ϳ95% identical to exon 1b and parts of the 2 flanking introns of the ␤3 gene ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Cloning and Functional Expression of Two Families of β-Subunits of the Large Conductance Calcium-activated K+ Channel

Uebele

Lagrutta

Wade

et al. 2000

Journal of Biological Chemistry

230

248

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We report here a characterization of two families of calcium-activated K ؉ channel ␤-subunits, ␤2 and ␤3, which are encoded by distinct genes that map to 3q26.2-27. A single ␤2 family member and four alternatively spliced variants of ␤3 were investigated. These subunits have predicted molecular masses of 27.1-31.6 kDa, share ϳ30 -44% amino acid identity with ␤1, and exhibit distinct but overlapping expression patterns. Coexpression of the ␤2 or ␤3a-c subunits with a BK ␣-subunit altered the functional properties of the current expressed by the ␣-subunit alone. The ␤2 subunit rapidly and completely inactivated the current and shifted the voltage dependence for activation to more polarized membrane potentials. In contrast, coexpression of the ␤3a-c subunits resulted in only partial inactivation of the current, and the ␤3b subunit conferred an apparent inward rectification. Furthermore, unlike the ␤1 and ␤2 subunits, none of the ␤3 subunits increased channel sensitivity to calcium or voltage. The tissue-specific expression of these ␤-subunits may allow for the assembly of a large number of distinct BK channels in vivo, contributing to the functional diversity of native BK currents.

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Section: Resultsmentioning

confidence: 99%

Cloning and Functional Expression of Two Families of β-Subunits of the Large Conductance Calcium-activated K+ Channel

Uebele

Lagrutta

Wade

et al. 2000

Journal of Biological Chemistry

230

248

View full text Add to dashboard Cite

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“…repressor factor and VDR (53,54). Moreover, recent studies have identified an important mechanism that could up-regulate EGFR expression in human ACF through enhanced Wnt/h-catenin signaling (55,56).…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Signaling Is Up-regulated in Human Colonic Aberrant Crypt Foci

et al. 2006

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Aberrant crypt foci (ACF) are collections of abnormal colonic crypts with heterogeneous molecular and pathologic characteristics. Large and dysplastic ACF are putative precursors of colon cancer with neoplastic risk related to increased proliferation. In this study, we examined the role of epidermal growth factor receptor (EGFR) signaling in regulating ACF proliferation. Using magnification chromoendoscopy, we collected large ACF with endoscopic features of dysplasia and separately biopsied adjacent mucosa. Transcript levels were measured by real-time PCR, proteins were assessed by Western blotting, and levels were expressed as fold changes of adjacent mucosa. K-ras and B-Raf mutations were assessed by PCR and Ras activation by the ratio Ras-GTP / (Ras-GTP + Ras-GDP). At the RNA level, 38% of ACF were hyperproliferative, with proliferating cell nuclear antigen (PCNA) mRNA z2-fold of adjacent mucosa. Hyperproliferative ACF had significantly increased mRNA levels of EGFR (6.0 F 1.7-fold), transforming growth factor-A (14.4 F 5.0-fold), heparin-binding EGF-like growth factor (4.5 F 1.4-fold), cyclin D1 (4.6 F 0.7-fold), and cyclooxygenase-2 (COX-2; 9.3 F 4.2-fold; P < 0.05). At the protein level, 46% of ACF were hyperproliferative (PCNA, 3.2 F 1.2-fold). In hyperproliferative ACF, 44% possessed significant increases in four EGFR signaling components: EGFR (9.5 F 1.3-fold), phosphoactive ErbB2 (2.6 F 0.4-fold), phosphoactive extracellular signal-regulated kinase (3.7 F 1.1-fold), and cyclin D1 (3.4 F 0.8-fold; P < 0.05). Ras was activated in 46% of ACF (3.2 F 0.4-fold; P < 0.05), but K-ras mutations were present in only 7% of ACF. In contrast to COX-2 mRNA, the protein was not increased in hyperproliferative ACF. In summary, we have shown that ACF with up-regulated PCNA possess increased EGFR signaling components that likely contribute to the enhanced proliferative state of

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“…After we obtained a cDNA clone, D40, that binds to GCF, we later discovered that the reported GCF cDNA clone is chimeric, consisting of two different cDNA fragments. One was derived from the GCF2 transcription factor and the other was from unrelated gene product with unknown function (Reed et al, 1998;Takimoto et al, 1999). D40 protein binds to the latter.…”

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confidence: 99%

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

et al. 2002

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We found a significant correlation between lung cancer in smokers and the expression of a human gene, D40, predominantly expressed in testis and cancers. In an attempt to clone a novel human gene, we screened a cDNA library derived from a human B cell line and obtained a cDNA clone that we refer to as D40. A search for public databases for sequence homologies showed that the D40 gene is identical to AF15q14. D40 mRNA is predominantly expressed in normal testis tissue. However, this gene is also expressed in various human tumour cell lines and primary tumours derived from various organs and tissues, such as lung cancer. We examined the relationship between D40 expression and clinico-pathological characteristics of tumours in primary lung cancer. D40 expression did not significantly correlate with either histological type or pathological tumour stage. However, D40 expression was observed more frequently in poorly differentiated tumours than in well or moderately differentiated ones. Furthermore, the incidence of D40 expression was significantly higher in tumours from patients who smoke than in those from non-smokers. D40/AF15q14 is the first gene in the cancer/testis family for which expression is related to the smoking habits of cancer patients.

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Molecular Cloning and Characterization of a Transcription Regulator with Homology to GC-binding Factor

Cited by 52 publications

References 38 publications

Cloning and Functional Expression of Two Families of β-Subunits of the Large Conductance Calcium-activated K+ Channel

Cloning and Functional Expression of Two Families of β-Subunits of the Large Conductance Calcium-activated K+ Channel

Epidermal Growth Factor Receptor Signaling Is Up-regulated in Human Colonic Aberrant Crypt Foci

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

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