Pescadillo, a novel cell cycle regulatory protein abnormally expressed in malignant cells

Using a culture model of glial tumorigenesis, we identified a novel gene th at was up regulated in malignant mouse astrocytes following the loss of p53 . The gene represents the murine homologue of pescadillo, an uncharacterize d gene that is essential for embryonic development in zebrafish, Pescadillo is a strongly conserved gene containing unique structural motifs such as a BRCA1 C-terminal domain, clusters of acidic amino acids and consensus moti fs for post translational modification by SUMO-1. Pescadillo displayed a di stinct spatial and temporal pattern of gene expression during brain develop ment, being detected in neural progenitor cells and postmitotic neurons. Al though it is not expressed in differentiated astrocytes in, vivo, the pesca dillo protein is dramatically elevated in malignant human astrocytomas, Yea st strains harboring temperature-sensitive mutations in the pescadillo gene were arrested in either G(1) or G(2) when grown in nonpermissive condition s, demonstrating that pescadillo is an essential gene in yeast and is requi red for cell cycle progression. Consistent with the latter finding, DNA syn thesis was only observed in mammalian cells expressing the pescadillo prote in. These results suggest that pescadillo plays a crucial role in cell prol iferation and may be necessary for oncogenic transformation and tumor progr ession.