UV light causes well-known symptoms of a stress response. One of the target molecules is cRaf, activated during UV exposure. Activation is mediated by reactive oxygen elicited by UV intracellularly.
We have identified the zinc-finger domain of cRaf as the site of action. As with PKC, the oxidation of thiol groups compromises the chelation of zinc ions and causes their release (Figure 3).
Both the modification of cysteine residues and relocation of zinc have been demonstrated by us, and retinol has been invoked as an enhancing cofactor. In distinction to PKC however, these biochemical events are not sufficient to induce cRaf kinase activity. This comes about by successive contact with activated ras.
We are conducting a multidisciplinary study, involving cellular, molecular and structural biological methods, as well as novel cell imaging techniques to solve these questions.
