Repressor roles for TCF-4 and Sfrp1 in Wnt signaling in breast cancer.

Mutations in Wnt pathway genes are rare in human breast cancer, yet activation of the pathway is evident from the misolocalization of beta-catenin. We searched for relationships in the expression of Wnt pathway genes and found that both secreted frizzled related protein 1 (Sfrp1) and TCF-4 transcripts were all highly downregulated in a common subset of breast cancers relative to normal breast tissue. Sfrp1 has been previously characterized as a Wnt inhibitor, and we found that interfering with its expression in the human mammary epithelial cell line MCF10A activated Wnt signaling.

Protein-protein interactions governing septin heteropentamer assembly and septin filament organization in Saccharomyces cerevisiae.

Mitotic yeast (Saccharomyces cerevisiae) cells express five related septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1) that form a cortical filamentous collar at the mother-bud neck necessary for normal morphogenesis and cytokinesis. All five possess an N-terminal GTPase domain and, except for Cdc10, a C-terminal extension (CTE) containing a predicted coiled coil. Here, we show that the CTEs of Cdc3 and Cdc12 are essential for their association and for the function of both septins in vivo.

Coupling morphogenesis to mitotic entry.

In eukaryotes, cyclin B-bound cyclin-dependent protein kinase 1 promotes mitotic entry but is held in check, in part, by Wee1 protein kinase. Timely mitotic entry in budding yeast requires inactivation of Swe1 (Wee1 ortholog). Perturbations of the septin collar at the bud neck lead to Swe1 stabilization, delaying the G(2)/M transition.

Targeting of Nir2 to lipid droplets is regulated by a specific threonine residue within its PI-transfer domain.

Nir2, like its Drosophila homolog retinal degeneration B (RdgB), contains an N-terminal phosphatidylinositol-transfer protein (PI-TP)-like domain. Previous studies have suggested that RdgB plays an important role in the fly phototransduction cascade and that its PI-transfer domain is critical for this function. In this domain, a specific mutation, T59E, induces a dominant retinal degeneration phenotype.

Dynamic localization of the Swe1 regulator Hsl7 during the Saccharomyces cerevisiae cell cycle.

In Saccharomyces cerevisiae, entry into mitosis requires activation of the cyclin-dependent kinase Cdc28 in its cyclin B (Clb)-associated form. Clb-bound Cdc28 is susceptible to inhibitory tyrosine phosphorylation by Swe1 protein kinase. Swe1 is itself negatively regulated by Hsl1, a Nim1-related protein kinase, and by Hsl7, a presumptive protein-arginine methyltransferase.