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01 October 2006

Signaling cascades in radiation-induced apoptosis: Roles of protein kinase C in the apoptosis regulation

Tetsuo Nakajima

Med Sci Monit 2006; 12(10): RA220-224 :: ID: 459205

Abstract

Apoptosis is a biologic mechanism for eliminating damaged cells from the cell population. Apoptosis
is known to be induced by irradiation and can prevent the development of disease states such as
carcinogenesis or abnormal tissue formation. On the other hand, if the mechanism is properly controlled,
radiotherapy can be used to kill cancer cells more effi ciently. Radiation-induced apoptosis is regulated by the balance between cellular anti-apoptotic and (pro-)apoptotic signals. Many regulators
of radiation-induced apoptosis have been identifi ed and analyzed. Protein kinase C (PKC) is a family of serine/threonine kinases and one of the regulators in radiation-induced apoptosis. PKC has some subtypes, each of whose functions has been analyzed in radiation-induced signaling cascades. It has been demonstrated that each of PKC subtypes has distinct functions in radiation- induced apoptosis. Moreover, some participants in PKC-related signaling cascades have been identifi ed in radiation-induced apoptosis. Interestingly, PKC-related signaling cascades have been found to be regulated in part by ATM (the gene that is mutated in the human genetic disorder
ataxia telangiectasia). ATM is a protein related to cell-cycle checkpoints and cell radiosensitivity,
and it also regulates radiation-induced apoptosis. This article reviews recent developments in the
understanding of radiation-induced apoptosis, focusing on PKC functions, and the relationship
with ATM.

Keywords: Apoptosis - radiation effects, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins - metabolism, DNA-Binding Proteins - metabolism, Protein Kinase C - metabolism, Protein-Serine-Threonine Kinases - metabolism, Radiation Tolerance - genetics, Signal Transduction - radiation effects, Tumor Suppressor Proteins - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750