identification of essential sequences for cellular localization in brms1 metastasis suppressor识别的基本序列brms1转移抑制基因的细胞定位.pdfVIP

Identification of Essential Sequences for Cellular Localization in BRMS1 Metastasis Suppressor ´ 1 ´ 2 1 ´ 1¤ Jose Rivera *, Diego Megıas , Carolina Navas , Jeronimo Bravo * ´ 1 Signal Transduction Group, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain, 2 Confocal Microscopy Unit, Centro Nacional de Investigaciones ´ Oncologicas, Madrid, Spain Abstract Background: Breast cancer metastasis suppressor 1 (BRMS1) reduces the number and the size of secondary tumours in a mouse model without affecting the growth of the primary foci upon its re-expression. Knockdown of BRMS1 expression associates with metastasis. The molecular details on BRMS1 mechanism of action include its ability to function as a transcriptional co-repressor and consistently BRMS1 has been described as a predominantly nuclear protein. Since cellular distribution could represent a potential mechanism of regulation, we wanted to characterize BRMS1 sequence motifs that might regulate its cellular distribution. According to its amino acids sequence, BRMS1 contain two putative nuclear localization signals, however none of them has been proved to work so far. Methodology/Principal Findings: By using well known in vivo assays to detect both nuclear import and export signal, we have characterized, in the present study, one functional nuclear localisation signal as necessary and sufficient to promote nuclear transport. Additionally, the outcome of a directed yeast two-hybrid assay identify