p73 Independent of c-Myc Represses Transcription of Platelet-derived Growth Factor β-Receptor through Interaction with NF-Y

Hackzell, Anders; Uramoto, Hidetaka; Izumi, Hiroto; Kohno, Kimitoshi; Funa, Keiko

doi:10.1074/jbc.m204483200

Cited by 31 publications

(34 citation statements)

References 36 publications

(24 reference statements)

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“…We previously found that levels of Myc and p73 increase following serum stimulation when they repress the promoter activity. So far of all cell-cycle regulating molecules investigated by us, only ∆Np73 has been shown to activate the promoter (Hackzell et al, 2002). The p53-mediated activation that we detected here is small yet significant and appears to involve the Sp1-binding site of the promoter.…”

Section: Discussionsupporting

confidence: 44%

“…We therefore tested whether p53 has any activity at all on the promoter. In a previous study, we showed that p73α bound NF-Y and repressed the promoter activity, but p53 did not (Hackzell et al, 2002). Careful evaluation of the effect of p53 on various PDGF β-receptor promoter constructs in 3T3 cells showed a small but significant increase in the activity (Fig.…”

Section: P53 Increases the Pdgf β-Receptor Promoter Activity Through mentioning

confidence: 99%

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pRb, Myc and p53 are critically involved in SV40 large T antigen repression of PDGF β-receptor transcription

Uramoto

Hackzell

Wetterskog

et al. 2004

Journal of Cell Science

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The expression of the PDGF β-receptor is tightly regulated during a normal cell cycle. c-Myc and p73α repress transcription of the receptor through interaction with NF-Y. In ST15A cells which stably express the temperature-sensitive SV40 large T antigen (LT) the receptor expression and ligand binding decreased under the permissive condition. Transient expression of the LT, but not small t, decreased the endogenous receptor expression at mRNA and protein levels in NIH3T3 cells but not in the myc-null HO15.19 cells. The wild-type LT, but not the various pRb or p53 binding defective LT mutants, represses the PDGF β-receptor promoter activity. Moreover, the inability of the LT-mediated repression in the myc-null cells, the Rb-null 3T3 cells, and the Saos-2 cells lacking pRb and p53, indicates that Myc, pRb and p53 are all necessary elements. PDGF β-receptor promoter-luciferase assays revealed that the CCAAT motif is important for the repression. Furthermore, p53 was found to increase the promoter activity mainly via the upstream Sp1 binding sites together with the CCAAT motif in the NIH 3T3 cells. This was confirmed by Schneider's Drosophila line (SL2) cells deficient in both endogenous NF-Y and Sp1. Chromatin immunoprecipitation using ST15A cells revealed that both LT and p53 bound the PDGF β-receptor promoter and the binding of p53 diminished when LT was expressed in the permissive condition. However, LT binds the promoter in the absence of pRb and p53 in Saos-2 cells stably expressing LT. These results suggest that LT binds the promoter and interferes with NF-Y and Sp1 to repress it in the presence of Myc, pRb and p53.

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Section: Discussionsupporting

confidence: 44%

Section: P53 Increases the Pdgf β-Receptor Promoter Activity Through mentioning

confidence: 99%

pRb, Myc and p53 are critically involved in SV40 large T antigen repression of PDGF β-receptor transcription

Uramoto

Hackzell

Wetterskog

et al. 2004

Journal of Cell Science

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“…The N-terminal deleted variants are disrupted in the transactivation (TA) domains, acting as dominant negative molecules by competing with the full-length isoforms for DNA-binding and oligomerisation (Nakagawara et al, 2002;Zaika et al, 2002). In our previous report, the C-terminal SAM domain of p73α was shown to bind NF-YB and NF-YC, thereby interfering with the NF-Y-mediated transactivation of the PDGFRB promoter (Hackzell et al, 2002). However, the mechanism for p73α repression of NF-Y activity has not been completely elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously shown that expression of platelet-derived growth factor β-receptor (PDGFRB) is controlled during the cell cycle and the increase in c-Myc and p73α following mitogenic stimulation represses the PDGF β-receptor promoter (Hackzell et al, 2002;Izumi et al, 2001;Oster et al, 2000;Uramoto et al, 2004). c-Myc and p73α bind NF-Y, thereby interfering with the transcription activation independently of each other.…”

Section: Introductionmentioning

confidence: 99%

p73 competes with co-activators and recruits histone deacetylase to NF-Y in the repression of PDGF β-receptor

Uramoto

Wetterskog

Hackzell

et al. 2004

Journal of Cell Science

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We investigated mechanisms of the p73α-mediated repression of the platelet-derived growth factor β-receptor (PDGFRB) promoter caused by its interaction with NF-Y. Treatment of cells with the histone deacetylase (HDAC) inhibitor, Trichostatin A, increases PDGFRB promoter activity through the CCAAT motif and counteracts the repression caused by p73α. Activation of the PDGFRB promoter by the co-activator p300 also occurs through the CCAAT motif. Expression of p73α counteracts both p300- and P/CAF-mediated activation of the PDGFRB promoter, and expression of p300 or P/CAF attenuates the p73α-mediated repression of the promoter activity. In concordance, p73α decreases the p300-mediated acetylation of NF-YC, p300 competes with p73α for binding NF-YB, and P/CAF competes with p73α for binding NF-YB and NF-YC. Furthermore, p73α, but not the oncogenic ΔNp73α, binds directly to HDAC1. We performed chromatin immunoprecipitation with antibodies against p73, ΔNp73, NFYB, p300 and HDAC1 at different periods after serum stimulation in serum-starved NIH3T3 cells. A marked decrease of ΔNp73, NF-YB and p300 was detected 6 hours after serum stimulation when the expression of PDGFRB decreased. Conversely, HDAC1 was found bound at its maximum and the anti-p73 detecting both TAp73 and ΔNp73 was found at all time points, indicating that p73, but not ΔNp73, remains bound at this time. Double immunofluorescence staining of TAp73 and HDAC1 revealed that both of these molecules exist in the nucleus at this time point, supporting the presence of endogenous interaction. These results suggest that p73 and ΔNp73 behave as physiological regulators for the transcription of the PDGFRB promoter.

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“…8, A and B). A similar effect of TSA on p73 repression of the platelet-derived growth factor ␤ receptor had been reported previously and shown to be mediated by the NF-YB factors (51). To further demonstrate involvement of NF-YB in p73-mediated hTERT promoter regulation, we used the characterized NF-YB1 and NF-YB2 shRNA vectors previously shown to abrogate expression of NF-YB factors in transient transfection experiments (Fig.…”

Section: P53-mediated Repression Of Htert Promoter Requires Distinct mentioning

confidence: 99%

Tumor Suppressors p53, p63TAα, p63TAy, p73α, and p73β Use Distinct Pathways to Repress Telomerase Expression

Yao¹,

Bellon²,

Shelton

et al. 2012

Journal of Biological Chemistry

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p73 Independent of c-Myc Represses Transcription of Platelet-derived Growth Factor β-Receptor through Interaction with NF-Y

Cited by 31 publications

References 36 publications

pRb, Myc and p53 are critically involved in SV40 large T antigen repression of PDGF β-receptor transcription

pRb, Myc and p53 are critically involved in SV40 large T antigen repression of PDGF β-receptor transcription

p73 competes with co-activators and recruits histone deacetylase to NF-Y in the repression of PDGF β-receptor

Tumor Suppressors p53, p63TAα, p63TAy, p73α, and p73β Use Distinct Pathways to Repress Telomerase Expression

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