The small heat-shock protein αB-crystallin promotes FBX4-dependent ubiquitination

Abstract

αB-Crystallin is a small heat-shock protein in which three serine residues (positions 19, 45, and 59) can be phosphorylated under various conditions. We describe here the interaction of αB-crystallin with FBX4, an F-box-containing protein that is a component of the ubiquitin-protein isopeptide ligase SCF (SKP1/CUL1/F-box). The interaction with FBX4 was enhanced by mimicking phosphorylation of αB-crystallin at both Ser-19 and Ser-45 (S19D/S45D), but not at other combinations. Ser-19 and Ser-45 are preferentially phosphorylated during the mitotic phase of the cell cycle. Also αB-crystallin R120G, a mutant found to co-segregate with a desmin-related myopathy, displayed increased interaction with FBX4. Both αB-crystallin S19D/S45D and R120G specifically translocated FBX4 to the detergentinsoluble fraction and stimulated the ubiquitination of one or a few yet unknown proteins. These findings implicate the involvement of αB-crystallin in the ubiquitin/proteasome pathway in a phosphorylation- and cell cycle-dependent manner and may provide new insights into the αB-crystallin-induced aggregation in desmin-related myopathy.