Misregulated RNA Pol II C-terminal domain phosphorylation results in apoptosis

Schauer, Tamás; Tombácz, István; Ciurciu, Anita; Komonyi, Orbán; Boros, Imre

doi:10.1007/s00018-009-8670-0

Cited by 10 publications

(8 citation statements)

References 30 publications

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“…In accordance with this, the human p53 protein has been reported to associate with coding regions of RNAPII-transcribed genes in a heterologous system32. It was previously shown that Dmp53 ( Drosophila melanogaster p53) was localised at transcriptionally active regions on the Drosophila polytene chromosomes and that the phosphorylation state of RPB1 CTD influenced its localisation33.…”

mentioning

confidence: 74%

Human p53 interacts with the elongating RNAPII complex and is required for the release of actinomycin D induced transcription blockage

Borsos

Huliák

Majoros

et al. 2017

Sci Rep

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The p53 tumour suppressor regulates the transcription initiation of selected genes by binding to specific DNA sequences at their promoters. Here we report a novel role of p53 in transcription elongation in human cells. Our data demonstrate that upon transcription elongation blockage, p53 is associated with genes that have not been reported as its direct targets. p53 could be co-immunoprecipitated with active forms of DNA-directed RNA polymerase II subunit 1 (RPB1), highlighting its association with the elongating RNA polymerase II. During a normal transcription cycle, p53 and RPB1 are localised at distinct regions of selected non-canonical p53 target genes and this pattern of localisation was changed upon blockage of transcription elongation. Additionally, transcription elongation blockage induced the proteasomal degradation of RPB1. Our results reveal a novel role of p53 in human cells during transcription elongation blockage that may facilitate the removal of RNA polymerase II from DNA.

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mentioning

confidence: 74%

Human p53 interacts with the elongating RNAPII complex and is required for the release of actinomycin D induced transcription blockage

Borsos

Huliák

Majoros

et al. 2017

Sci Rep

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“…Overexpression or silencing of CTDP1 may inhibit its associated regulation mechanisms. Schauer et al (16) found that FCP1 misregulation, whether FCP1 overexpression or silencing, induced p53-dependent and enhanced levels of caspase-mediated apoptosis in Drosophila melanogaster. The present study also found that CTDP1 silencing induced an increase in the apoptotic rate of GC cells.…”

Section: Discussionmentioning

confidence: 99%

Carboxy-terminal domain phosphatase 1 silencing results in the inhibition of tumor formation ability in gastric cancer cells

Yang

Wang

et al. 2015

Oncology Letters

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Abstract. Gastric cancer (GC), one of the most malignant types of cancer, is the second greatest cause of cancer-associated mortality worldwide. Novel therapeutic targets for GC treatment are therefore urgently required. Carboxy-terminal domain phosphatase 1 (CTDP1) has a crucial role in the regulation of gene expression. However, to the best of our knowledge, the role of CTDP1 in GC has not previously been explored. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was used to detect CTDP1 messenger RNA expression in various GC cell lines. CTDP1 was subsequently silenced in GC cells by lentivirus-mediated small interfering RNA (siRNA) infection, and the effects of CTDP1 inhibition on cell proliferation were evaluated by cell number counting, cell cycle analysis with propidium iodide staining and fluorescence-activated cell sorting (FACS) analysis, apoptotic rate with Annexin V staining and FACS analysis, as well as colony formation assay in GC cells. The results revealed that CTDP1 was highly expressed in certain GC cell lines and lentivirus-mediated siRNA infection was able to effectively silence CTDP1 expression in GC cells. CTDP1 inhibition decreased cell proliferation, arrested the cell cycle at G0/G1 phase and increased cell apoptosis in GC cells. Furthermore, the colony formation ability of GC cells was also suppressed by silencing CTDP1. Taken together these results indicated that CTDP1 has a significant role in the tumor formation ability of GC cells and is a novel and promising therapeutic target for the treatment of GC.

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“…Many studies have demonstrated that death-receptor, mitochondria and endoplasmic reticulum played an important role in apoptosis (8,9). The activation of effector caspases such as caspase-3 and -7 by initiator caspases (caspase-8 and -9) are responsible for the cleavage of cellular substrates degrading the chromosomes into nucleosomal fragments during apoptosis (10,11). Two major pathways are involved in cell apoptosis; the death receptor pathway and the mitochondria-dependent pathway.…”

Section: Introductionmentioning

confidence: 99%

Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways

Chen¹

2011

Int J Oncol

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Abstract. Cantharidin (CTD) is a traditional Chinese medicine and an effective component isolated from blister beetle, and it has been demonstrated to have anticancer, antibiotic, antivirus activities and immune-regulated functions. It has been reported that CTD induces cell cycle arrest and apoptosis in many cancer cell types. However, there are no reports showing that CTD would induce cell cycle arrest and apoptosis in human colorectal cancer colo 205 cells. In this study, we studied colo 205 cells which were treated with CTD and demonstrated its molecular mechanisms in apoptosis. CTD induced growth inhibition, G2/M phase arrest and apoptosis in colo 205 cells. The IC 50 is 20.53 µM in CTD-treated colo 205 cells. DAPI/TUNEL double staining and Annexin V assays were used to confirm the apoptotic cell death in colo 205 cells after CTD exposure. CTD caused G2/M arrest, down-regulated CDK1 activity, decreased Cyclin A, Cyclin B, CDK1 and increased CHK1 and p21 protein levels. Colorimetric assays also indicated that CTD triggered activities of casapse-8, -9 and -3 in colo 205 cells. Moreover, CTD increased ROS production and decreased the level of mitochondrial membrane potential (ΔΨm) in colo 205 cells. Consequently, CTD-induced growth inhibition was significantly attenuated by N-acetylcysteine (NAC, a scavenger). CTD stimulated the protein levels of Fas/CD95, the caspase-3 active form, cytochrome c and Bax, but suppressed the protein levels of pro-caspase-8, pro-caspase-9 and Bcl-2, determined by Western blot analysis. Based on our observations, we suggest that CTD is able to induce G2/M phase arrest and apoptosis in colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways.

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Misregulated RNA Pol II C-terminal domain phosphorylation results in apoptosis

Cited by 10 publications

References 30 publications

Human p53 interacts with the elongating RNAPII complex and is required for the release of actinomycin D induced transcription blockage

Human p53 interacts with the elongating RNAPII complex and is required for the release of actinomycin D induced transcription blockage

Carboxy-terminal domain phosphatase 1 silencing results in the inhibition of tumor formation ability in gastric cancer cells

Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways

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