Requirement of ATM in UVA-induced Signaling and Apoptosis

Yiguo Zhang,Wei-Ya Ma,Akira Kaji,Ann M Bode,Zigang Dong

doi:10.1074/jbc.m110245200

Abstract

Solar UVA, but not UVC, reaches the earth's surface and therefore is an important etiological factor for the induction of human skin cancer. ATM kinase is an important regulator of cell survival and cell cycle checkpoints. Here, we observe that UVA, unlike UVC, triggers ATM kinase activity, and the activation may occur through reactive oxygen species produced after irradiation of cells with UVA. We also show that ATM activation is involved in the apoptotic response to UVA but not UVC. Furthermore, we provide evidence that ATM-dependent p53 and c-Jun N-terminal kinase (JNK) pathways are linked to UVA-induced apoptosis. On the other hand, UVC-induced apoptosis occurs through ATR-dependent p53 phosphorylation as well as the JNK pathway. Therefore, these results suggest that ATM, like p53, is involved in the UVA-induced apoptosis to suppress carcinogenesis.

Highlights

The solar UV light that reaches the earth’s surface is divided into ultraviolet A (UVA) (320 – 400 nm) and ultraviolet B (UVB) (290 –320 nm) [1, 2]
Similar activation of caspase-3 by Ultraviolet C (UVC) occurred in both Atmϩ and AtmϪ cell lines (Fig. 1C, lower panel). These results suggest that ATM appears to be required for induction of apoptosis by UVA but not UVC
ATM kinase was shown to be activated in the cellular responses to double strand breaks (DSBs) [14, 29] and such breaks induced by ionizing radiation (IR) [12, 13, 30], radiomimetic drugs [12], or arsenite [31] but not to UVB/ UVC or base-damaging agents [11, 13, 17, 28, 30], suggesting that ATM may act in response to DSBs

Summary

Introduction

The solar UV light that reaches the earth’s surface is divided into ultraviolet A (UVA) (320 – 400 nm) and ultraviolet B (UVB) (290 –320 nm) [1, 2]. UVA constitutes over 90% of solar UV at ground level and can penetrate the skin Both in vitro and in vivo experiments clearly confirmed that UVA, like UVB and UVC, is a mutagen and carcinogen [1, 2]. Carcinogenesis appears to arise as a consequence of a combination of disturbances in signal transduction pathways that control cell cycle checkpoints, cell survival, arrest, and apoptosis [2,3,4] Such disturbed signaling may result from mutation of key regulatory genes. ATM was shown to be activated in the cellular response to ionizing radiation (IR), but not to UVC exposure (10 –13), and the activated ATM was recruited to double strand breaks (DSBs) for repair [14] These findings are frequently cited as evidence that UV-induced signal transduction does not require ATM activation. We provide evidence that ATM is activated by UVA, but not UVC, and is involved in the cellular decision to trigger p53- and c-Jun N-terminal kinase (JNK)-dependent apoptotic pathways in response to UVA

Methods

Results

Conclusion