UV-INDUCED SIGNAL-TRANSDUCTION

Irradiation of cells with short wavelength ultraviolet light (UVA, B a nd C) induces the transcription of many genes. The program overlaps wi th that induced by oxidants and alkylating agents and has both protect ive and other functions. Genes transcribed in response to UV irradiati on include genes encoding transcription factors, growth factors, prote ases and viral proteins. While the transcription of transcription fact or encoding genes is initiated in minutes after UV irradiation (immedi ate response genes) and depends exclusively on preformed proteins, the transcription of protease encoding genes occurs only many hours after UV irradiation. Transcription factors controlling the activity of imm ediate response genes are activated by protein kinases belonging to th e group of proline directed protein kinases immediately after UV irrad iation. Experimenter evidence suggests that these kinases are activate d in UV irradiated cells through pathways which are used by growth fac tors. In fact, the first cellular reaction detectable in UV irradiated cells is the phosphorylation of several growth factor receptors at ty rosine residues. This phosphorylation does not depend on UV induced DN A damage, but is due to an inhibition of the activity of tyrosine phos phatases. In contrast, for late cellular reactions to UV, an obligator y role of DNA damage in transcribed regions of the genome can be demon strated. Thus, UV is absorbed by several target molecules relevant for cellular signaling, and it appears that numerous signal transduction pathways are stimulated The combined action of these pathways establis hes the genetic program that determines the fate of UV irradiated cell s.