Pitx2a Binds to Human Papillomavirus Type 18 E6 Protein and Inhibits E6-mediated P53 Degradation in HeLa Cells

Wei, Qize

doi:10.1074/jbc.m502974200

Cited by 31 publications

(32 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of exogenously added recombinant p53 on the complex formation was easily assessed in this assay because HeLa cells, which are HPV-E6 transformed, have low levels of p53 expression (Wei, 2005). As shown in Figure 1c, increasing amounts of His-p53 increased both the amount of CstF1 'pulled down' by GST-BARD1 (upper panel, lanes 1-8) and the amount of BARD1 'pulled down' by GST-CstF1 (lower panel, lanes 1-8), indicating that p53 stabilized the CstF1/BARD1 complex.…”

Section: Resultsmentioning

confidence: 99%

p53 inhibits mRNA 3′ processing through its interaction with the CstF/BARD1 complex

et al. 2011

View full text Add to dashboard Cite

The mechanisms involved in the p53-dependent control of gene expression following DNA damage have not been completely elucidated. Here, we show that the p53 C terminus associates with factors that are required for the ultraviolet (UV)-induced inhibition of the mRNA 3 0 cleavage step of the polyadenylation reaction, such as the tumor suppressor BARD1 and the 3 0 processing factor cleavage-stimulation factor 1 (CstF1). We found that p53 can coexist in complexes with CstF and BARD1 in extracts of UV-treated cells, suggesting a role for p53 in mRNA 3 0 cleavage following DNA damage. Consistent with this, we found that p53 inhibits 3 0 cleavage in vitro and that there is a reverse correlation between the levels of p53 expression and the levels of mRNA 3 0 cleavage under different cellular conditions. Supporting these results, a tumor-associated mutation in p53 not only decreases the interaction with BARD1 and CstF, but also decreases the UV-induced inhibition of 3 0 processing, all of which is restored by wild-type-p53 expression. We also found that p53 expression levels affect the polyadenylation levels of housekeeping genes, but not of p21 and c-fos genes, which are involved in the DNA damage response (DDR). Here, we identify a novel 3 0 RNA processing inhibitory function of p53, adding a new level of complexity to the DDR by linking RNA processing to the p53 network.

show abstract

Section: Resultsmentioning

confidence: 99%

p53 inhibits mRNA 3′ processing through its interaction with the CstF/BARD1 complex

et al. 2011

View full text Add to dashboard Cite

show abstract

“…27 In this regard, it is interesting that Pitx2 has been shown to bind to HPV type 18 E6 protein and inhibit p53 degradation in vitro, leading to the accumulation of functional p53 protein and the induction of cell-cycle arrest in HeLa cells. 30 Whether Pitx2 also transcriptionally activates p53 remains to be determined, but the two family members at least share functional equivalence in terms of p53 function. Here, we have demonstrated that hPitx1 binds directly to the p53 promoter in vitro and in vivo resulting in the transcriptional activation of the p53 gene.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional activation of p53 by Pitx1

Lobie

2007

Cell Death Differ

View full text Add to dashboard Cite

Little is known about factors that stimulate transcription of the p53 tumor suppressor gene. Here, we report that the human pituitary homeobox 1 (hPitx1) transcription factor increases the expression of p53 at the mRNA and protein levels in human mammary carcinoma (MCF-7) cells. Increased p53 mRNA expression was due to activation of the p53 promoter by hPitx1. hPitx1 bound directly to the p53 promoter and functionally utilized two hPitx1 consensus elements. The predominant consensus element utilized by hPitx1 to stimulate p53 transcription was located within the first exon of the p53 gene. A hPitx1 mutant (hPitx1-R141P) acting as a dominant inhibitor repressed p53 transcription. Forced expression of hPitx1 resulted in cell-cycle arrest and p53-dependent apoptosis in p53-replete MCF-7 cells. Furthermore, hPitx1 stimulated the transcription of p53 target genes involved in cell-cycle arrest and apoptosis (p21 and PTGF-b), again in a p53-dependent manner. Depletion of endogenous hPitx1 by small interfering RNA (siRNA) in MCF-7 cells resulted in decreased basal expression of p53 and consequently of p21 and placental transforming growth factor b (PTGF-b). Depletion of p53 by siRNA dramatically attenuated hPitx1-induced apoptosis in MCF-7 cells. Thus, p53 is a direct transcriptional target gene of hPitx1. This observation is concordant with the recent identification of hPitx1 as a tumor suppressor gene.

show abstract

“…b OSRGA, POS and UMR106: p53 status was defined by immunocytochemistry using a p53 antibody specific for the wild-type (wt) protein. For other cell lines, the p53 status was already defined in the literature (Diller et al, 1990;Casey et al, 1991;Chandar et al, 1992;Florenes et al, 1994;Wei, 2005). c STAT5 activation was studied after 15 min of OSM treatment by western blotting experiment using a P-STAT5 antibody.…”

Section: Proapoptotic Effects Of Osm On Osteosarcoma Cells C Chipoy Ementioning

confidence: 99%

“…The role of p53 in sensitization to apoptosis by OSM was then confirmed by the screening of cell lines with different p53 status (Figure 6d, Table 1 and Supplementary Figure 2 for ROS, ST2 and MG63 cells). Indeed, the combination OSM þ Sts did not induce apoptosis on cell lines which have a defective p53 (mutated or null), like MG63, SaOS2 and MNNG-HOS human osteosarcoma cell lines (Diller et al, 1990;Casey et al, 1991;Chandar et al, 1992;Wei, 2005). The resistant U2OS cells are known to express wild-type p53, but inactivated by an excess of its negative regulatory partner mdm2 (Florenes et al, 1994) and/or loss of its activator p14 ARF (Stott et al, 1998).…”

Section: Stat5 Is Necessary For Apoptosis Induced By Osm þ Stsmentioning

confidence: 99%

Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53

et al. 2007

View full text Add to dashboard Cite

Oncostatin M (OSM), a cytokine of the interleukin-6 family, induces growth arrest and differentiation of osteoblastic cells into glial-like/osteocytic cells. Here, we asked whether OSM regulates apoptosis of normal or transformed (osteosarcoma) osteoblasts. We show that OSM sensitizes cells to apoptosis induced by various death inducers such as staurosporine, ultraviolet or tumor necrosis factor-a. Apoptosis is mediated by the mitochondrial pathway, with release of cytochrome c from the mitochondria to the cytosol and activation of caspases-9 and -3. DNA micro-arrays revealed that OSM modulates the expression of Bax, Bad, Bnip3, Bcl-2 and Mcl-1. Pharmacological inhibitors, dominant-negative signal transducer and activator of transcriptions (STATs), stable RNA interference and knockout cells indicated that the transcription factors p53 and STAT5, which are activated by OSM, are implicated in the sensitization to apoptosis, being responsible for Bax induction and Bcl-2 reduction, respectively. These results indicate that, in addition to growth arrest and induced differentiation, OSM also sensitizes normal and transformed osteoblasts to apoptosis by a mechanism implicating (i) activation and nuclear translocation of STAT5 and p53 and (ii) an increased Bax/Bcl-2 ratio. Therefore, association of OSM with kinase inhibitors such as Sts represents new therapeutic opportunities for wild-type p53 osteosarcoma.

show abstract

Pitx2a Binds to Human Papillomavirus Type 18 E6 Protein and Inhibits E6-mediated P53 Degradation in HeLa Cells

Cited by 31 publications

References 49 publications

p53 inhibits mRNA 3′ processing through its interaction with the CstF/BARD1 complex

p53 inhibits mRNA 3′ processing through its interaction with the CstF/BARD1 complex

Transcriptional activation of p53 by Pitx1

Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53

Contact Info

Product

Resources

About