Loss of p14(ARF) confers resistance to heat shock- and oxidative stress-mediated cell death by upregulating β-catenin

Alexander Damalas; Georgia Velimezi; Alexander Kalaitzakis; Michalis Liontos; Athanasios G Papavassiliou; Vassilis Gorgoulis; Charalampos Angelidis

doi:10.1002/ijc.25510

Loss of p14(ARF) confers resistance to heat shock- and oxidative stress-mediated cell death by upregulating β-catenin

Int J Cancer. 2011 Apr 15;128(8):1989-95. doi: 10.1002/ijc.25510.

Authors

Alexander Damalas¹, Georgia Velimezi, Alexander Kalaitzakis, Michalis Liontos, Athanasios G Papavassiliou, Vassilis Gorgoulis, Charalampos Angelidis

Affiliation

¹ Department of Biology, University of Ioannina, Ioannina, Greece.

PMID: 20549705
DOI: 10.1002/ijc.25510

Abstract

The p14(ARF) is a key tumor suppressor induced mainly by oncogenic stimuli. Although p14(ARF) does not seem to respond to DNA damage, there are very few data regarding its role in other forms of stress, such as heat shock (HS) and oxidative stress (OS). Here, we report that suppression of p14(ARF) increased resistance to cell death when cells were treated with H(2) O(2) or subjected to HS. In this setting, protection from cell death was mediated by elevated levels and activity of β-catenin, as downregulation of β-catenin alleviated the protective role of p14(ARF) silencing. Moreover, Hsp70 was shown to regulate β-catenin protein levels by interacting with p14(ARF) , suggesting that Hsp70, p14(ARF) and β-catenin form a regulatory network. This novel pathway triggers cell death signals when cells are exposed to HS and OS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis*
Blotting, Western
Cell Proliferation
Flow Cytometry
Gene Expression Regulation, Neoplastic
HSP72 Heat-Shock Proteins / genetics
HSP72 Heat-Shock Proteins / metabolism*
Heat-Shock Response*
Humans
Immunoprecipitation
Luciferases / metabolism
Neoplasms / genetics
Neoplasms / metabolism
Neoplasms / pathology
Oxidative Stress*
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Tumor Suppressor Protein p14ARF / antagonists & inhibitors
Tumor Suppressor Protein p14ARF / genetics
Tumor Suppressor Protein p14ARF / metabolism*
Up-Regulation
beta Catenin / genetics
beta Catenin / metabolism*

Substances

CTNNB1 protein, human
HSP72 Heat-Shock Proteins
RNA, Messenger
RNA, Small Interfering
Tumor Suppressor Protein p14ARF
beta Catenin
Luciferases