Diacylglycerol Signaling

Chapter 12
Protein Kinase C, p53, and DNA Damage
Kiyotsugu Yoshida
Abstract The cellular response to genotoxic stress that damages DNA includes cell
cycle arrest, activation of DNA repair, and in the event of irreparable damage, induction
of apoptosis. However, the signals that determine cell fate, that is, survival or
apoptosis, are largely unknown. The protein kinase C (PKC) has been implicated
in many important cellular processes, including regulation of apoptotic cell death.
In particular, d isoform of PKC (PKCd) contributes to the induction of apoptosis
in response to DNA damage. When cells encounter genotoxic stress, certain
sensors for DNA lesions activate PKCd. PKCd is then proteolytically activated
by caspase-3, and the cleaved catalytic fragment translocates to the nucleus and
induces apoptosis. Importantly, nuclear targeting of PKCd is essential for induction
of apoptosis. In this regard, PKCd regulates transcription by phosphorylating
various transcription factors, including the p53 tumor suppressor that is critical for
cell cycle arrest and apoptosis in response to DNA damage. These findings collectively
support a pivotal role for PKCd in the induction of apoptosis with significant
impact. This review is focused on the current views regarding the regulation of cell
fate by PKCd signaling and p53 in response to DNA damage.
Keywords Apoptosis • DNA damage • Nuclear targeting • PKC • p53
• Phosphorylation
12.1 Introduction
Genotoxic stress that damages DNA induces cell cycle arrest, activation of DNA
repair, and in the event of irreparable damage, induction of apoptosis. The decision
of cells either to repair DNA lesions and continue through the cell cycle or to
K. Yoshida (*)
Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
e-mail: yos.mgen@mri.tmd.ac.jp
M.G. Kazanietz (ed.), Protein Kinase C in Cancer Signaling and Therapy,
Current Cancer Research, DOI 10.1007/978-1-60761-543-9_12,
© Springer Science+Business Media, LLC 2010
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