FLASH meets nuclear bodies: CD95 receptor signals via a nuclear pathway.

The CD95 receptor signals via assembly of a multi-protein complex termed death-inducing signaling complex (DISC) which triggers activation of receptor-bound caspase-8/FLICE molecules. Most cells (type II cells) depend on a mitochondrial amplification pathway to commit apoptosis upon CD95 activation. The caspase-8-binding protein FLICE-associated huge protein (FLASH) has been previously implicated in the regulation of caspase-8 activation at the DISC.

FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies.

Caspase-8-binding protein FLICE-associated huge protein (FLASH) has been proposed to regulate death receptor CD95-induced apoptosis through facilitating caspase-8 activation at the death-inducing signaling complex. Here, we found that FLASH interacts with the PML nuclear body component Sp100 and predominantly resides in the nucleus and nuclear bodies (NBs). In response to CD95 activation, FLASH leaves the NBs and translocates into the cytoplasm where it accumulates at mitochondria.

Nucleo-cytoplasmic distribution of beta-catenin is regulated by retention.

beta-catenin is the central signalling molecule of the canonical Wnt pathway, where it activates target genes in a complex with LEF/TCF transcription factors in the nucleus. The regulation of beta-catenin activity is thought to occur mainly on the level of protein degradation, but it has been suggested that beta-catenin nuclear localization and hence its transcriptional activity may additionally be regulated via nuclear import by TCF4 and BCL9 and via nuclear export by APC and axin. Using live-cell microscopy and fluorescence recovery after photobleaching (FRAP), we have directly analysed the impact of these factors on the subcellular localization of beta-catenin, its nucleo-cytoplasmic shuttling and its mobility within the nucleus and the cytoplasm.