Role of p53 in Regulating Radiation Responses

Abstract

p53 is known as the guardian of the genome and plays various roles in DNA damage and cancer suppression. The p53 gene was found to express multiple p53 splice variants (isoforms) in a physiological, tissue-dependent manner. The various genes that up- and down-regulated p53 are involved in cell viability, senescence, inflammation, and carcinogenesis. Moreover, p53 affects the radioadaptive response. Given that several studies have already been published on p53, this review presents its role in the response to gamma irradiation by interacting with MDM2, NF-κB, and miRNA, as well as in the inflammation processes, senescence, carcinogenesis, and radiation adaptive responses. Finally, the potential of p53 as a biomarker is discussed.

Keywords: adaptive response; carcinogenesis; p53; radiation.

Figure 1

Schema of the human p53 gene structure: (A): alternative splicing sites (α, β, and γ) and promoters (P1 and P2) are marked. (B): Schema of the human p53 protein isoforms can be expressed by the human p53 gene. TAD, transcription activation domain; PRD, proline-rich domain; HD, hinge domain; and OD, oligomerization domain.

Figure 2

Scheme of the association between p53 and MDM2 in irradiation. DNA damage induced by ionizing radiation induces p53. DNAPK can also induce p53 expression. MDM2 is present in the cytoplasm and nucleus and suppresses p53 function. P53 expresses p21, GADD45A, and CDKN1A.

Figure 3

Scheme of the association between p53 and NF-κB in irradiation. ATM and DNAPK are expressed by ionizing radiation causing DNA damage. PIDD is involved in the NF-κB expression. ROS and ATM induced IKK1 and IKK2. IκB-α degrades and activates NF-κB. TNFα may also activate NF-κB. p53 and NF-κB may be dependent or independent.

Figure 4

Scheme of the association between p53 and miRNAs in irradiation MiRNAs induce p53 or suppress p53 function.