Signaling cascades in radiation-induced apoptosis: roles of protein kinase C in the apoptosis regulation.
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 efficiently. Radiation-induced apoptosis is regulated by the balance between cellular anti-apoptotic and (pro-)apoptotic signals. Many regulators of radiation-induced apoptosis have been identified 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 identified 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.
Nakajima
Tetsuo
T
Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa, Inage-ku, Chiba, Japan. otetsu@nirs.go.jp
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D011493:Protein Kinase C / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D015398:Signal Transduction / Q000528:radiation effects*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C