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Hsp72 mediates TAp73α anti-apoptotic effects in small cell lung carcinoma cells.

Nyman U, Muppani NR, Zhivotovsky B, Joseph B - J. Cell. Mol. Med. (2011)

Bottom Line: However, the precise mechanism by which TAp73α exerts its pro-survival effect is yet unclear.Finally, we revealed that TAp73β counteracts the anti-apoptotic effect of TAp73α by preventing Hsp72 induction.Our results thus provide additional evidence for the potential oncogenic role of TAp73α, and extend the understanding of the mechanism for its anti-apoptotic effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.

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Hsp72 expression prevents TAp73β-induced mitochondrial dysfunction and Bax activation. (A, B) H82 cells were co-transfected with EGFP, Hsp72 vector and empty vector or TAp73β. Treatment and staining were performed as described in Figure 4A and B, and analysis was carried out using microscopy (A) and FACS analysis (B). (C, D) H82 cells were transfected, treated and stained as described in Figure 4C and D. Images are representatives of three independent experiments. Figures are mean ± S.D. of three independent experiments, where *P < 0.05, **P < 0.01 and ***P < 0.001.
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fig05: Hsp72 expression prevents TAp73β-induced mitochondrial dysfunction and Bax activation. (A, B) H82 cells were co-transfected with EGFP, Hsp72 vector and empty vector or TAp73β. Treatment and staining were performed as described in Figure 4A and B, and analysis was carried out using microscopy (A) and FACS analysis (B). (C, D) H82 cells were transfected, treated and stained as described in Figure 4C and D. Images are representatives of three independent experiments. Figures are mean ± S.D. of three independent experiments, where *P < 0.05, **P < 0.01 and ***P < 0.001.

Mentions: TAp73 isoforms have been shown to induce apoptosis via Puma-mediated Bax activation [30]. To investigate whether the protective effect of Hsp72 overexpression upon TAp73β-enhanced drug-induced apoptosis is exerted upstream of apoptosis-related mitochondrial events, H82 cells were co-transfected with TAp73β and Hsp72 expression vectors. Introduction of Hsp72 greatly diminished TAp73β-induced ΔΨm disruption upon VP16 treatment, as shown by both cell counting in microscope (Fig. 5A) and FACS analysis (Fig. 5B) of TMRE– cells. In addition, TAp73β-induced Bax activation was reduced upon introduction of Hsp72, as depicted by confocal imaging (Fig. 5C) and FACS analysis (Fig. 5D). Hence, TAp73β-mediated Bax activation and disruption of ΔΨm in response to VP16 can be prevented by the simultaneous expression of Hsp72.


Hsp72 mediates TAp73α anti-apoptotic effects in small cell lung carcinoma cells.

Nyman U, Muppani NR, Zhivotovsky B, Joseph B - J. Cell. Mol. Med. (2011)

Hsp72 expression prevents TAp73β-induced mitochondrial dysfunction and Bax activation. (A, B) H82 cells were co-transfected with EGFP, Hsp72 vector and empty vector or TAp73β. Treatment and staining were performed as described in Figure 4A and B, and analysis was carried out using microscopy (A) and FACS analysis (B). (C, D) H82 cells were transfected, treated and stained as described in Figure 4C and D. Images are representatives of three independent experiments. Figures are mean ± S.D. of three independent experiments, where *P < 0.05, **P < 0.01 and ***P < 0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373366&req=5

fig05: Hsp72 expression prevents TAp73β-induced mitochondrial dysfunction and Bax activation. (A, B) H82 cells were co-transfected with EGFP, Hsp72 vector and empty vector or TAp73β. Treatment and staining were performed as described in Figure 4A and B, and analysis was carried out using microscopy (A) and FACS analysis (B). (C, D) H82 cells were transfected, treated and stained as described in Figure 4C and D. Images are representatives of three independent experiments. Figures are mean ± S.D. of three independent experiments, where *P < 0.05, **P < 0.01 and ***P < 0.001.
Mentions: TAp73 isoforms have been shown to induce apoptosis via Puma-mediated Bax activation [30]. To investigate whether the protective effect of Hsp72 overexpression upon TAp73β-enhanced drug-induced apoptosis is exerted upstream of apoptosis-related mitochondrial events, H82 cells were co-transfected with TAp73β and Hsp72 expression vectors. Introduction of Hsp72 greatly diminished TAp73β-induced ΔΨm disruption upon VP16 treatment, as shown by both cell counting in microscope (Fig. 5A) and FACS analysis (Fig. 5B) of TMRE– cells. In addition, TAp73β-induced Bax activation was reduced upon introduction of Hsp72, as depicted by confocal imaging (Fig. 5C) and FACS analysis (Fig. 5D). Hence, TAp73β-mediated Bax activation and disruption of ΔΨm in response to VP16 can be prevented by the simultaneous expression of Hsp72.

Bottom Line: However, the precise mechanism by which TAp73α exerts its pro-survival effect is yet unclear.Finally, we revealed that TAp73β counteracts the anti-apoptotic effect of TAp73α by preventing Hsp72 induction.Our results thus provide additional evidence for the potential oncogenic role of TAp73α, and extend the understanding of the mechanism for its anti-apoptotic effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.

Show MeSH
Related in: MedlinePlus