The intronic region of Fbxl12 functions as an alternative promoter regulated by UV irradiation

Abstract

The ubiquitin ligases, SCF complexes, consist of Cul1, Skp1, Rbx1 and the substrate recognition components F-box proteins. Previous studies have reported that one of these F-box proteins, Fbl12, which is produced by Fbxl12 gene, regulates both cell cycle and differentiation. In this paper, we show that the intronic region of Fbxl12 gene acts as an alternative promoter and induces expression of a short form of Fbl12 that lacks F-box domain (Fbl12ΔF). We also found that UV irradiation increases Fbl12ΔF mRNA in cells. Finally, Fbl12ΔF may promote the subcellular localization of Fbl12 from nucleus to cytoplasm through their binding. Our data provide the possibility that Fbl12ΔF induced by alternative promoter controls the SCFFbl12 activity in response to UV stimulation.

SCFFbl12 Increases p21Waf1/Cip1 Expression Level through Atypical Ubiquitin Chain Synthesis

“…Recently, we reported that UV irradiation induces Fbl12⌬F transcription via the alternative promoter, leading to an involvement of Fbl12 regulation (49). Since overexpression of Fbl12⌬F does not affect the cellular proliferation, it is possible that Fbl12-related pathways are linked to UV-induced DNA damage response.…”