Format

Send to

Choose Destination
Oncogene. 2004 Apr 29;23(20):3721-5.

p73-alpha is capable of inducing scotin and ER stress.

Author information

1
Biochemistry Laboratory, IDI-IRCCS, Department of Experimental Medicine and Biochemical Sciences, University of Rome 'Tor Vergata', 00133 Rome, Italy.

Abstract

p73, like its family member p53, can induce programmed cell death following DNA damage. Here, we report that this mechanism also involves endoplasmic reticulum (ER) stress and the transactivation of scotin, a protein identified recently as a p53 target able to induce ER stress. By using Tet-On inducible cell lines (Saos 2 osteosarcoma cells that lack p53), we observed that TAp73alpha elicits significant alterations in the morphology of the ER system, namely in the fine subcellular localization of calnexin. We found that both TAp73alpha and p53 are strong inducers of scotin. On the other hand, the transcriptionally deficient short isoforms DeltaNp73alpha did not upregulate the steady-state mRNA level of scotin, as evaluated by real-time RT-PCR. Following the induction of scotin, ER staining with calnexin showed evidence of morphological alteration, with variations in the intracellular concentration of free calcium, visualized by fluo-3 staining. The induction of ER stress by p73 was further supported by the transcriptional induction of Gadd 153, a transcription factor induced under ER stress conditions. In conclusion, the data reported indicate the ability of TAp73alpha and p53 (not DeltaNp73alpha) to elicit scotin transactivation and ER stress. This molecular mechanism might contribute to the effector events inducing apoptosis downstream of p73.

PMID:
15116103
DOI:
10.1038/sj.onc.1207342
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center