SerpinB2 is involved in cellular response upon UV irradiation

Abstract

Ultraviolet light induced pyrimidine dimer is a helix distortion DNA damage type, which recruits repair complexes. However, proteins of these complexes that take part in both DNA damage recognition and repair have been well-described, the regulation of the downstream steps of nucleotide excision repair (NER) have not been clearly clarified yet. In a high-throughput screen, we identified SerpinB2 (SPB2) as one of the most dramatically upregulated gene in keratinocytes following UV irradiation. We found that both the mRNA and the protein levels of SPB2 were increased upon UV irradiation in various cell lines. Additionally, UV damage induced translocation of SPB2 from the cytoplasm to the nucleus as well as the damage induced foci formation of it. Here we show that SPB2 co-localizes with XPB involved in the NER pathway at UV-induced repair foci. Finally, we demonstrated that UV irradiation promoted the association of SPB2 with ubiquitylated proteins. In basal cell carcinoma tumour cells, we identified changes in the subcellular localization of SPB2. Based on our results, we conclude that SPB2 protein has a novel role in UV-induced NER pathway, since it regulates the removal of the repair complex from the damaged site leading to cancerous malformation.

SerpinB10, a Serine Protease Inhibitor, Is Implicated in UV-Induced Cellular Response

“…Our results and recent studies also showed that UV irradiation induces robust gene expression changes in the Hker E6SFM keratinocyte cell line [19][20][21][22]. Among the upregulated genes, we identified several members of the B clade of the Serpin superfamily, including SerpinB2, SerpinB10, and SerpinB13 [19].…”

“…In this study, we investigated a novel, yet-to-be-characterized function of the SPB10 protein following UV irradiation. Our preliminary microarray data indicated that members of the SerpinB family could play a role in UV-induced cellular responses [19,20]. We revealed an increase in the mRNA level of SPB10 upon UV irradiation in three skinderived cell lines (Hker E6SFM, HaCaT, and A375).…”

“…The members of the SerpinB (SPB) family are mainly intracellular proteins, and it has been demonstrated that they can regulate various processes, such as inflammation, immune function, mucous production, apoptosis, tumor metastasis, and autoimmunity [23][24][25][26][27]. Nonetheless, only a limited amount of data are available concerning their regulatory role in DNA repair [19,20,[28][29][30].…”

Cyclobutane pyrimidine dimers from UVB exposure induce a hypermetabolic state in keratinocytes via mitochondrial oxidative stress

“…UVA (315–400 nm) mainly induces oxidative stress and DNA damage via reactive oxygen species (ROS) generation; UVB exposure (280–315 nm) mostly causes direct DNA damage through the production of intra-strand DNA base cross-linking, including cyclobutane pyrimidine dimers (CPDs) and (6–4) pyrimidine-pyrimidone photoproducts (6–4)PPs] and their Dewar isomers [ 19 ]. In humans, UVB-induced photoproducts are repaired by the evolutionary conserved but slow nucleotide excision repair (NER) mechanism [ [20] , [21] , [22] ]. UV irradiation can reach the surface of an organism.…”

Emerging Roles of Post-Translational Modifications in Nucleotide Excision Repair

“…In response to UV irradiation, the precise function of these factors ensures the preservation of genome integrity in a coordinated spatiotemporal manner, thereby significantly contributing to the prevention of cancerous malformations. We have already shown that SerpinB2 can play a role in the regulation of the NER pathway through the XPB protein as well as the ubiquitin network, and this function is altered in tumor cells [98]. Hence, being aware of any malfunction of even one of these factors can contribute to the better understanding the molecular background of the tumor.…”