α-tubulin on death row

Cytotoxic T-cells (CTLs) kill virus-infected cells and tumour cells by releasing granules containing proteins that induce apoptosis. One of these - granzyme B - is thought to act by cleaving caspases, critical apoptotic enzymes whose cleavage activates the death program. Granzyme B can kill cells even when caspases are inhibited, however, and so it must have other targets. Chris Bleackley and co-workers now reveal that one of these is the cytoskeleton (see p. 858). They have analysed cell lysates treated with granzyme B by mass spectrometry and identify α-tubulin as one of the proteins cleaved. Moreover, they show that α-tubulin is cleaved in vivo in cells undergoing CTL-induced apoptosis and that this can be blocked by inhibiting granzyme B activity (but not caspases). Bleackley and co-workers have pinned down the cleavage site to an aspartate residue (D38) in a C-terminal sequence that is highly conserved among tubulin isoforms. Since this region binds to proteins that regulate microtubule dynamics and the cleaved α-tubulin partitions predominantly into the soluble pool, the authors propose that an important apoptotic effect of granzyme B is microtubule disassembly.