Protein Kinases and Transcription Factors Activation in Response to UV-Radiation of Skin: Implications for Carcinogenesis

Abstract

Solar ultraviolet (UV) radiation is an important environmental factor that leads to immune suppression, inflammation, photoaging, and skin carcinogenesis. Here, we reviewed the specific signal transduction pathways and transcription factors involved in the cellular response to UV-irradiation. Increasing experimental data supporting a role for p38, MAPK, JNK, ERK1/2, and ATM kinases in the response network to UV exposure is discussed. We also reviewed the participation of NF-κB, AP-1, and NRF2 transcription factors in the control of gene expression after UV-irradiation. In addition, we discussed the promising chemotherapeutic intervention of transcription factors signaling by natural compounds. Finally, we focused on the review of data emerging from the use of DNA microarray technology to determine changes in global gene expression in keratinocytes and melanocytes in response to UV treatment. Efforts to obtain a comprehensive portrait of the transcriptional events regulating photodamage of intact human epidermis after UV exposure reveals the existence of novel factors participating in UV-induced cell death. Progress in understanding the multitude of mechanisms induced by UV-irradiation could lead to the potential use of protein kinases and novel proteins as specific targets for the prevention and control of skin cancer.

Ultraviolet Radiation in Wound Care: Sterilization and Stimulation

“…The biological effect induced by UV radiation activates different signal pathways in a time-, dose-, and wavelength-specific manner. 9,10 The hypothesis is that UV wavelengthspecific action spectrum is stemmed from distinct direct damages to various biomolecules. 9 The major cellular chromophores that absorb in the UVB range are nucleic acids (DNA and RNA) and proteins (mainly tryptophan and tyrosine amino acids) and other biomolecules like NADH, quinones, flavins, porphyrins, 7-dehydrocholesterol, and urocanic acid.…”

“…9,10 The hypothesis is that UV wavelengthspecific action spectrum is stemmed from distinct direct damages to various biomolecules. 9 The major cellular chromophores that absorb in the UVB range are nucleic acids (DNA and RNA) and proteins (mainly tryptophan and tyrosine amino acids) and other biomolecules like NADH, quinones, flavins, porphyrins, 7-dehydrocholesterol, and urocanic acid. Several molecular changes and signaling pathways are activated upon UV irradiation and the eventual fate of the UV-exposed cell will be decided by the severity of the damage.…”

“…21,49 p38 is an important inducer of cell cycle arrest and UVinduced double-strand breaks have also been shown to activate p38 through the DNA damage sensors ATM and Rad3-related protein kinase (ATR). 9,50 It is essential to realize that cell survival or death mechanisms are often concomitantly activated after UV and share common molecular mediators. Therefore, depending on the severity of the insult (i.e., the UV dose), the cellular background, and additional microenvironmental factors, the balance between cell survival and death signals will eventually decide on the fate of the irradiated cell.…”

“…Exposure to UV is known to induce clustering of some kinds of cell surface receptors and to transduce some cell survival and proliferation signals. 9,38 Activation of intracellular signaling pathways in response to UV radiation induces various transcription factors that transactivate genes involved in DNA repair, DNA synthesis, transcription, and cell cycle regulation.…”

Transcriptional and Secretomic Profiling of Epidermal Cells Exposed to Alpha Particle Radiation

“…They can elicit a series of inflammatory response cascades that can affect the gene and protein microenvironment. Keratinocytes have been shown to respond to radiation insults such as UV radiation with the production of proinflammatory mediators and gene responses [reviewed in 11,12]. Therefore they serve as a pertinent cell-type to monitor effects associated with α-particle radiation exposures.…”