Degradation of the transcriptional repressor Capicua is regulated by RTK-dependent subcellular localization

Stanislav Shvartsman
Genomics Institute, Princeton University, Princeton

Abstract

The transcriptional repressor Capicua (Cic) controls multiple aspects of Drosophila embryogenesis and has been implicated in vertebrate development and human diseases. Receptor tyrosine kinases (RTK) can antagonize Cic-dependent gene repression, but the mechanisms responsible for this effect are not fully understood. Based on genetic and imaging studies in the early Drosophila embryo, we found that RTK signaling can increase the rate of Cic degradation by changing its subcellular localization. We propose that Cic is degraded predominantly in the cytoplasm and show that RTK signaling reduces the stability of Cic by controlling the rates of its nucleocytoplasmic transport. This model accounts for the experimentally observed spatiotemporal dynamics of Cic in the early embryo and may explain RTK-dependent de-repression of Cic target genes in multiple contexts.

This work is done together with Oliver Grimm, Victoria Sanchez, Jordi Casanova, and Eric Wieschaus.








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