Hsp72 mediates TAp73α anti-apoptotic effects in small cell lung carcinoma cells.
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.
Affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.Show MeSH
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Mentions: TAp73 isoforms have been shown to induce apoptosis via Puma-mediated Bax activation . 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.
Affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.