Review Article
The BRCA1 Breast Cancer Suppressor: Regulation of Transport, Dynamics, and Function at Multiple Subcellular Locations
Figure 6
BRCA1 nuclear export stimulates targeting to the centrosome. BRCA1 is known to be exported from nucleus to cytoplasm by the CRM1 export receptor [48, 72]. (a) CRM1 has been implicated in centrosome function and when overexpressed as a YFP fusion is detectable at the centrosome by microscopy (CRM1 shown in green, centrosome marker pericentrin shown in red). (b) The inhibition of CRM1 activity by treatment with leptomycin B (LMB) results in reduced staining of endogenous BRCA1 at the centrosome. (c) A range of recent FRAP experiments [46] showed that mutation of the BRCA1 NES caused an increase in BRCA1 exchange rate at the centrosome, consistent with reduced retention. (d) Moreover, mutation of the NES abolished the ability of ectopic wild-type BRCA1 to control rampant centrosome amplification after exposure of HCC1937 breast cancer cells to ionising radiation. This implies that CRM1 contributes to the role of BRCA1 in tight regulation of centrosome duplication. These data were originally published in Brodie and Henderson [46], © the American Society for Biochemistry and Molecular Biology, and reproduced with permission.
