Roles for the dynactin complex in the glucocorticoid receptor signaling pathway

Regulation of translocation of transcriptional activators from the cytoplasm into the nucleus is an essential process in signal transduction pathways. Targeted proteolysis of signaling molecules usually participates in termination of signal transduction. Various molecules are incorporated into large complexes that mediate both activation and termination of signaling pathways. I found that dynactin complex, a major activator of the microtubule-based motor cytoplasmic dynein, modulates GR-dependent signal transduction. Disruption of either dynactin complex organization or microtubule organization causes constitutive translocation of GR into the nucleus, suggesting that GR is tethered to microtubules via dynactin complex. Dynactin cargo-binding subunits appear to be involved in regulation of GR metabolism via their interaction with the COP9 signalosome. In conclusion, dynactin plays two important regulatory roles in the GR signaling by regulating the nucleocytoplasmic partitioning and the turnover of GR.