Nuclear trafficking of pro-apoptotic kinases in response to DNA damage.

Abstract

The cellular response to genotoxic stress includes cell-cycle arrest, activation of DNA repair and induction of apoptosis. However, the signals that determine cell fate are largely unknown. Recent studies have shown that several pro-apoptotic kinases, including protein kinase C (PKC)delta, Abelson murine leukemia viral oncogene homolog 1 (c-Abl) and dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2), undergo nuclear-cytoplasmic shuttling in response to DNA damage. Importantly, whereas precise regulation for the shuttling of these kinases remains uncertain, this mechanism has consequences for induction of apoptosis and implies that proper localization is central to the function of pro-apoptotic kinases. This review highlights recent progress demonstrating that the nuclear targeting of kinases is a novel and essential regulatory mechanism that directly influences the induction of apoptosis in response to DNA damage. The potential implications for novel therapies are also discussed.

• Authors: Kiyotsugu Yoshida
• Journal: Trends in molecular medicine (Trends Mol Med) Vol. 14 Issue 7 Pg. 305-13 (Jul 2008) ISSN: 1471-4914 [Print] England
• PMID: 18539531 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Dyrk kinase
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-abl
• Protein Serine-Threonine Kinases
• Protein Kinase C-delta

Topics

• Active Transport, Cell Nucleus (physiology)
• Animals
• Apoptosis (physiology)
• Cell Nucleus (metabolism)
• DNA Damage (physiology)
• Humans
• Protein Kinase C-delta (metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Protein Transport (physiology)
• Protein-Tyrosine Kinases (metabolism)
• Proto-Oncogene Proteins c-abl (metabolism)