Soaking up stress

Text by Rabiya S. Tuma [email protected] Soaking up stress O n page 115, Ku and Omary add one more function to keratin’s expanding repertoire. In addition to acting as a structural protein in liver cells, keratin 8 (K8) apparently absorbs excess phosphorylation during stress and thus reduces the likelihood of apoptosis. Humans who carry a G61C polymorphism in K8 are predisposed to liver disease when exposed to insults such as infection. Unlike keratin-associated disorders in skin, these K8 variants do not appear to cause disease directly by decreasing the mechanical strength of cells. In fact, Ku and Omary found that mouse hepatocytes expressing G61C had normal mechanical strength, suggesting that the G61C polymorphism was affecting another stress response process. G61C interfered with phosphorylation at serine-73 (S73), which is one of two sites in K8 that are phosphorylated by stress-activated kinases during apoptosis. When stress kinases were activated, cells expressing G61C or S73A K8 proteins were more likely to die than those with wild-type K8. Moreover, the duration and degree of phosphorylation of other stress kinase substrates increased in the mutant cells, relative to control cells. The researchers conclude that K8 soaks up excess phosphorylation activity under stress conditions and thus hinders cell entry into apoptosis. Because S73 is conserved in several other keratins, Ku and Omary propose that the keratin-as-sponge function may be shared by other intermediate fi laments, as previously suggested for neurofi laments.