Abstract
In the framework of space flight, the risk of radiation carcinogenesis is considered a “red” risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a wide range of cell processes, including cell survival, proliferation, and differentiation. Among the CREB-related nuclear transcription factors, NF-κB and p53 have a relevant role in cell response to ionising radiation. Their expression and function can decide the fate of the cell by choosing between death or survival. The aim of this review was to define the role of the CREB/ATF family members and the related transcription factors in the response to ionising radiation of human haematological malignancies and solid tumours.
Highlights
Outside of the Earth’s protective magnetosphere, crews are exposed to galactic cosmic rays (GCR) and solar proton events (SPE) that occur when particles emitted by the sun, mostly protons, become accelerated in the interplanetary space due to a coronal mass ejection shock [1]
Cells can escape apoptotic death through activation of various survival factors. One of these factors is cyclic AMP response element-binding protein (CREB), which is upregulated in various tumours treated with radiotherapy. This CREB upregulation leads to increased cell proliferation, reduced apoptosis, and enhanced cell migration and contributes to metastatic transformation of cells, as well as to angiogenesis
Along with CREB, activating transcription factor (ATF) and Nuclear factor-κB (NF-κB) are upregulated in different types of malignancies
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Due to the lack of human epidemiological data related to the types of radiation found in space, the current research utilises a translational approach which includes advanced human cell-based model systems exposed to space radiation simulants connected with human molecular pathways [6]. This approach allows relating the biological effects of space radiation to effects from similar exposure to ground-based gamma rays and X-rays to extrapolate the results to large human epidemiological cohorts [6,7]. The present review is focused on the complex biochemical interactions of the CREB/ATF family members and the related transcription factors in the response to ionising radiation of human haematological malignancies and solid tumours
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