Bidirectional SV40 Transcription Mediated by Tandem Sp1 Binding Interactions

Gidoni, David; Kadonaga, James T.; Barrera-Saldaña, Hugo A.; Takahashi, K.; Chambon, Pierre; Tjian, Robert

doi:10.1126/science.2996137

Cited by 378 publications

(222 citation statements)

References 31 publications

(50 reference statements)

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“…It binds to GC-rich sequences such as GC-boxes (Gidoni et al, 1985) and basic transcription elements (Imataka et al, 1992). Additionally, Sp1 binding sites are found in the promoters of many housekeeping genes (Black and Azizkhan-Clifford, 1999).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide

et al. 2003

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Temozolomide (TMZ, 3,-as-tetrazine-8-carboxamide) is a new alkylating agent with promising antitumour efficacy for malignant gliomas. The resistance of tumour cells to TMZ is primarily associated with levels of the alkylguanine alkyltransferase (AGT). O 6 -benzylguanine (O 6 -BG), an inhibitor for AGT, reduced resistance to TMZ. Recently, it has been demonstrated that chemosensitivity of tumour cells is related to a decline in telomerase activity. However, it is unknown if TMZ sensitivity of malignant glioma cells correlates with telomerase. In this study, using malignant glioma cells with low levels of AGT (U373-MG and U87-MG) and high levels of AGT (T98G), we investigated the association among AGT, telomerase, and TMZ sensitivity. U373-MG and U87-MG cells were sensitive to TMZ (IC 50 for a 2-day treatment ¼ 100 mM), while T98G cells were resistant to TMZ (IC 50 for a 2-day treatment 4500 mM). Treatment with TMZ (100 mM) suppressed telomerase activity in U373-MG and U87-MG cells in a time-dependent manner, but not in T98G cells. The downregulation of telomerase activity in U373-MG and U87-MG cells was due to inhibition of the human telomerase reverse-transcriptase (hTERT) gene expression at the transcriptional level. This inhibitory effect was induced by interfering with transcription factor Sp1 binding sites of the hTERT core promoter. Interestingly, O 6 -BG not only sensitised T98G cells to TMZ, but also suppressed telomerase activity. These findings suggest that response of malignant glioma cells to TMZ can be monitored by reduction in telomerase activity. Therefore, quantification of telomerase activity during or after treatment with TMZ may be a useful marker to detect treatment efficacy.

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Section: Discussionmentioning

confidence: 99%

Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide

et al. 2003

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“…It has been found that promoters with multiple Sp1-binding sites may be very sensitive to mutations in a single Sp1-binding site (35,36), which may dramatically reduce their activity. In these cases, minor changes in Sp1 levels can severely affect activity of such promoters.…”

Section: Discussionmentioning

confidence: 99%

Myc represses the p21 ^(WAF1/CIP1) promoter and interacts with Sp1/Sp3

Gartel

Goufman

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

378

288

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“…1; refs. 3,[6][7][8][9]. The majority of TATA-less genes have multiple Sp1 sites in the proximal promoter region, and more than half of expressed genes are TATA-less (10).…”

Section: ¶-(G/t)gggcgg(g/a)(g/a)(g/t)-3 ¶] Via Threementioning

confidence: 99%

Phosphorylation of Sp1 in Response to DNA Damage by Ataxia Telangiectasia-Mutated Kinase

Olofsson

Kelly

Kim

et al. 2007

Molecular Cancer Research

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Sp1, a transcription factor that regulates expression of a wide array of essential genes, contains two SQ/TQ cluster domains, which are characteristic of ATM kinase substrates. ATM substrates are transducers and effectors of the DNA damage response, which involves sensing damage, checkpoint activation, DNA repair, and/or apoptosis. A role for Sp1 in the DNA damage response is supported by our findings: Activation of ATM induces Sp1 phosphorylation with kinetics similar to H2AX; inhibition of ATM activity blocks Sp1 phosphorylation; depletion of Sp1 sensitizes cells to DNA damage and increases the frequency of double strand breaks. We have identified serine 101 as a critical site phosphorylated by ATM; Sp1 with serine 101 mutated to alanine (S101A) is not significantly phosphorylated in response to damage and cannot restore increased sensitivity to DNA damage of cells depleted of Sp1. Together, these data show that Sp1 is a novel ATM substrate that plays a role in the cellular response to DNA damage. (Mol Cancer Res 2007;5(12):1319 -30)

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Bidirectional SV40 Transcription Mediated by Tandem Sp1 Binding Interactions

Cited by 378 publications

References 31 publications

Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide

Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide

Myc represses the p21 ^(WAF1/CIP1) promoter and interacts with Sp1/Sp3

Phosphorylation of Sp1 in Response to DNA Damage by Ataxia Telangiectasia-Mutated Kinase

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Bidirectional SV40 Transcription Mediated by Tandem Sp1 Binding Interactions

Cited by 378 publications

References 31 publications

Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide

Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide

Myc represses the p21 (WAF1/CIP1) promoter and interacts with Sp1/Sp3

Phosphorylation of Sp1 in Response to DNA Damage by Ataxia Telangiectasia-Mutated Kinase

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Myc represses the p21 ^(WAF1/CIP1) promoter and interacts with Sp1/Sp3