Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

Lee, Te-Hsiu; Chuang, Li‐Yeh; Hung, Wen‐Chun

doi:10.1038/sj.onc.1203715

Cited by 61 publications

(35 citation statements)

References 43 publications

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“…Recent studies show that HDAC1 might be recruited to the proximal region of the p21 promoter by Sp1 or, alternatively, to the distal region of the p21 promoter by other transcriptional regulators such as NRs and c-Jun (19,(41)(42)(43)(44). Induction of p53 in response to DNA-damaging agents could result in the formation of p53 and Sp1 complexes and, simultaneously, dissociate HDAC1 from the COOH terminus of Sp1 (20,28,33,45).…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Cyclin-Dependent Kinase Inhibitor p21WAF1/Cip1 Gene by Zac1 through the Antagonistic Regulators p53 and Histone Deacetylase 1 in HeLa Cells

Liu

Chan

Lin

et al. 2008

Molecular Cancer Research

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Zac1 is a novel seven -zinc finger protein which possesses the ability to bind specifically to GC-rich DNA elements. Zac1 not only promotes apoptosis and cell cycle arrest but also acts as a transcriptional cofactor for p53 and a number of nuclear receptors. Our previous study indicated that the enhancement of p53 activity by Zac1 is much more pronounced in HeLa cells compared with other cell lines tested. This phenomenon might be due to the coactivator effect of Zac1 on p53 and the ability of Zac1 to reverse E6 inhibition of p53. In the present study, we showed that Zac1 acted synergistically with either p53 or a histone deacetylase inhibitor, trichostatin A, to enhance p21 WAF1/Cip1 promoter activity. We showed that Zac1 physically interacted with some nuclear receptor corepressors such as histone deacetylase 1 (HDAC1) and mSin3a, and the induction of p21 WAF1/Cip1 gene and protein by Zac1 was suppressed by either overexpressing HDAC1 or its deacetylase-dead mutant. In addition, our data suggest that trichostatin A -induced p21 WAF1/Cip1 protein expression might be mediated through a p53-independent and HDAC deacetylaseindependent pathway. Taken together, our data suggest that Zac1 might be involved in regulating the p21 WAF1/Cip1 gene and protein expression through its protein-protein interaction with p53 and HDAC1 in HeLa cells.

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Section: Discussionmentioning

confidence: 99%

Modulation of the Cyclin-Dependent Kinase Inhibitor p21WAF1/Cip1 Gene by Zac1 through the Antagonistic Regulators p53 and Histone Deacetylase 1 in HeLa Cells

Liu

Chan

Lin

et al. 2008

Molecular Cancer Research

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“…Cells were received a second transfection after 12 h and maintained in 10% fetal calf serum medium for another 60 h. Effect of siRNA on cell cycle-distribution was studied by flow cytometry as described previously. 25 …”

Section: Sirna Treatment and Cell Growth Assaymentioning

confidence: 99%

Jab1 is overexpressed in human breast cancer and is a downstream target for HER-2/neu

et al. 2008

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“…ERK phosphorylation of Sp1 C-terminus is reported to regulate the binding of co-repressors (SMRT, NcoR and BcoR) to Sp1 N-terminal inhibitory domain. 35 We propose that phosphorylation at Threonine-739 facilitates sequential phosphorylation of the β-TrCP-site followed by enhanced cleavage of the Sp1 inhibitory domain. This scenario infers that ERK induced Sp1 phosphorylation is at odds with sumoylation, since N-terminal cleavage removes the SUMO-conjugating KRL-16.…”

confidence: 99%

Phosphorylation mediates Sp1 coupled activities of proteolytic processing, desumoylation and degradation

Spengler

Guo²,

Brattain³

2008

Cell Cycle

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Cell signaling pathways induce Sp1 phosphorylation, which allows for the upregulation of Sp1-dependent genes that control cell growth, cell cycle progression, survival and tumorigenesis. Sp1 activity is under constitutive repression through the sumoylation of Lysine-16, and Lysine-16 dependent N-terminal cleavage relieves this repression. The present investigation probes further into the mechanisms of Sp1 processing, desumoylation and degradation to reveal that phosphorylation is the major driving force behind these coupled activities. The first 7 amino acid residues of Sp1 enhance the accessibility of Lysine-16 to the homologous modifiers SUMO-1 and ubiquitin; and Serine-7 specifically enhances ubiquitinylation. Our data show that Serine-59 regulates Sp1 proteolytic processing, and thereby provides a mechanism for the upregulation of Sp1-dependent transcription by CyclinA/cdk2 phosphorylation of Serine-59. Sp1 activators, forskolin and PMA, enhance Sp1 processing in MCFE cells through distinct signaling pathways. PKC, ERK and ERBB2 kinase inhibitors suppress PMA induction of Sp1 and the specific isozyme PKCα enhances Sp1 cleavage. Sp1 contains several NFκB2-like proteolytic processing components including a functional phosphorylation-dependent β-TrCP binding motif. From these data, we propose a model by which cell cycle and mitotic kinases induce Sp1 proteolytic processing resulting in a desumoylated, derepressed and unstable Sp1 product.

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Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

Cited by 61 publications

References 43 publications

Modulation of the Cyclin-Dependent Kinase Inhibitor p21WAF1/Cip1 Gene by Zac1 through the Antagonistic Regulators p53 and Histone Deacetylase 1 in HeLa Cells

Modulation of the Cyclin-Dependent Kinase Inhibitor p21WAF1/Cip1 Gene by Zac1 through the Antagonistic Regulators p53 and Histone Deacetylase 1 in HeLa Cells

Jab1 is overexpressed in human breast cancer and is a downstream target for HER-2/neu

Phosphorylation mediates Sp1 coupled activities of proteolytic processing, desumoylation and degradation

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