A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines

Hess, Gerard F.; Drong, Roger F.; Weiland, Katherine L.; Slightom, Jerry L.; Sclafani, Robert A.; Hollingsworth, Robert E.

doi:10.1016/s0378-1119(98)00094-8

Cited by 65 publications

(50 citation statements)

References 21 publications

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“…In addition, the protein kinase CDC7, which is involved in regulating coupling cell-cycle regulation and genome duplication, is overexpressed highly in T265 cells. This is consistent with data implicating overexpression of CDC7 in hyper-proliferation and neoplastic transformation in a range of tumor types (Hess et al, 1998).…”

Section: Cell Cyclesupporting

confidence: 92%

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

et al. 2004

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AbstractcDNA microarrays were utilized to identify abnormally expressed genes in a malignant peripheral nerve sheath tumor (MPNST)-derived cell line, T265, by comparing the mRNA abundance profiles with that of normal human Schwann cells (nhSCs). The findings characterize the molecular phenotype of this important cell-line model of MPNSTs, and elucidate the contribution of Schwann cells in MPNSTs. In total, 4608 cDNA sequences were screened and hybridizations replicated on custom cDNA microarrays. In order to verify the microarray data, a large selection of differentially expressed mRNA transcripts were subjected to semi-quantitative reverse transcription PCR (LightCycler). Western blotting was performed to investigate a selection of genes and signal transduction pathways, as a further validation of the microarray data. The data generated from multiple microarray screens, semi-quantitative RT-PCR and Western blotting are in broad agreement. This study represents a comprehensive gene-expression analysis of an MPNST-derived cell line and the first comprehensive global mRNA profile of nhSCs in culture. This study has identified ~900 genes that are expressed abnormally in the T265 cell line and detected many genes not previously reported to be expressed in nhSCs. The results provide crucial information on the T265 cells that is essential for investigation using this cell line in experimental studies in neurofibromatosis type I (NF1), and important information on normal human Schwann cells that is applicable to a wide range of studies on Schwann cells in cell culture.

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Section: Cell Cyclesupporting

confidence: 92%

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

et al. 2004

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“…Human Cdc7 is overexpressed in many transformed cell lines as well as in many tumor specimens, but this overexpression does not always correlate with hyperproliferation (69). It is possible that huCdc7 overexpression is associated with neoplastic transformation.…”

Section: A 63-bp Promoter Dna Segment Highly Conserved Between Human mentioning

confidence: 99%

A 63-Base Pair DNA Segment Containing an Sp1 Site but Not a Canonical E2F Site Can Confer Growth-dependent and E2F-mediated Transcriptional Stimulation of the Human ASKGene Encoding the Regulatory Subunit for Human Cdc7-related Kinase

Yamada

Sato

Taniyama

et al. 2002

Journal of Biological Chemistry

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Cdc7-Dbf4 kinase complexes, conserved widely in eukaryotes, play essential roles in initiation and progression of the S phase. Cdc7 kinase activity fluctuates during cell cycle, and this is mainly the result of oscillation of expression of the Dbf4 subunit. Therefore, it is crucial to understand the mechanisms of regulation of Dbf4 expression. We have isolated and characterized the promoter region of the human ASK gene encoding Dbf4-related regulatory subunit for human Cdc7 kinase. We have identified a 63-base pair ASK promoter segment, which is sufficient for mediating growth stimulation. This minimal promoter segment (MP), containing an Sp1 site but no canonical E2F site, can be activated by ectopic E2F expression as well. Within the 63-base pair region, the Sp1 site as well as other elements are essential for stimulation by growth signals and by E2F, whereas an AT-rich sequence proximal to the coding region may serve as an element required for suppression in quiescence. Gel shift assays in the presence of an antibody demonstrate the presence of E2F1 in the protein-DNA complexes generated on the MP segment. However, the complex formation on MP was not competed by a DHFR promoter fragment, known to bind to E2F, nor by a consensus E2F binding oligonucleotide. Gel shift assays with point mutant MP fragments indicate that a non-canonical E2F site in the middle of this segment is critical for generation of the E2F complex. Our results suggest that E2F regulates the ASK promoter through an atypical mode of recognition of the target site.

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“…Overexpression of Cdc7-ASK occurs in various types of cancer (Hess et al 1998;Nambiar et al 2007;Bonte et al 2008;Clarke et al 2009;Kulkarni et al 2009) and often correlates with poor prognosis, suggesting that deregulated Cdc7 kinase activity may promote survival of cancer cells and tumor progression. Recently, some small molecule inhibitors of Cdc7 kinase activity have been developed and are being tested in clinical trials as candidate anti-cancer drugs (Ito et al 2008;Montagnoli et al 2008;Vanotti et al 2008;Ermoli et al 2009).…”

mentioning

confidence: 99%

ATR–Chk1–APC/C^Cdh1-dependent stabilization of Cdc7–ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress

et al. 2013

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Cdc7 kinase regulates DNA replication. However, its role in DNA repair and recombination is poorly understood. Here we describe a pathway that stabilizes the human Cdc7-ASK (activator of S-phase kinase; also called Dbf4), its regulation, and its function in cellular responses to compromised DNA replication. Stalled DNA replication evoked stabilization of the Cdc7-ASK (Dbf4) complex in a manner dependent on ATR-Chk1-mediated checkpoint signaling and its interplay with the anaphase-promoting complex/cyclosome Cdh1 (APC/C Cdh1 ) ubiquitin ligase. Mechanistically, Chk1 kinase inactivates APC/C Cdh1 through degradation of Cdh1 upon replication block, thereby stabilizing APC/C Cdh1 substrates, including Cdc7-ASK (Dbf4). Furthermore, motif C of ASK (Dbf4) interacts with the N-terminal region of RAD18 ubiquitin ligase, and this interaction is required for chromatin binding of RAD18. Impaired interaction of ASK (Dbf4) with RAD18 disables foci formation by RAD18 and hinders chromatin loading of translesion DNA polymerase h. These findings define a novel mechanism that orchestrates replication checkpoint signaling and ubiquitin-proteasome machinery with the DNA damage bypass pathway to guard against replication collapse under conditions of replication stress.

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A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines

Cited by 65 publications

References 21 publications

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

A 63-Base Pair DNA Segment Containing an Sp1 Site but Not a Canonical E2F Site Can Confer Growth-dependent and E2F-mediated Transcriptional Stimulation of the Human ASKGene Encoding the Regulatory Subunit for Human Cdc7-related Kinase

ATR–Chk1–APC/C^Cdh1-dependent stabilization of Cdc7–ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress

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A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines

Cited by 65 publications

References 21 publications

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells

A 63-Base Pair DNA Segment Containing an Sp1 Site but Not a Canonical E2F Site Can Confer Growth-dependent and E2F-mediated Transcriptional Stimulation of the Human ASKGene Encoding the Regulatory Subunit for Human Cdc7-related Kinase

ATR–Chk1–APC/CCdh1-dependent stabilization of Cdc7–ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress

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ATR–Chk1–APC/C^Cdh1-dependent stabilization of Cdc7–ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress