hob1+, the fission yeast homolog of Bin1, is dispensable for endocytosis or actin organization, but required for the response to starvation or genotoxic stress

Transformation-selective apoptotic program triggered by farnesyltransferase inhibitors requires Bin1

“…These findings identify Bin1 as a second element with RhoB that is part of a cell death process linked to transformed cell pathophysiology. RhoB has important functions in stress signaling (Prendergast, 2001) and recent genetic investigations in fission yeast support a similar role in stress signaling for Bin1 (Routhier et al, 2003). Thus, the specific requirements for RhoB and Bin1 in FTIinduced apoptosis may reflect broader roles for these genes in a unique stress signaling process.…”

“…Tumor size was measured by caliper and tumor volume was computed as described in the Materials and Methods. The data represent the average and standard mean error of the tumor volume as computed at the times indicated RVS167, but instead display defects in stress responses triggered by starvation or DNA damage (Routhier et al, 2003).…”

“…Budding yeast studies in particular suggest an important role for the actin cytoskeleton as a key site of action for BAR adapter proteins (Breton and Aigle, 1998;Balguerie et al, 1999;Colwill et al, 1999). However, Bin1 appears to have functions that differ from and/or extend beyond those defined for amphiphysin and the Rvs proteins, as suggested, for example, by (i) the nuclear localization of certain Bin1 isoforms and their functional interaction with nuclear Myc and Abl proteins (Kadlec and Pendergast, 1997;Wechsler-Reya et al, 1997;Elliott et al, 1999), (ii) the lack of endocytosis defects in Bin1 -/-cells (A Muller et al, manuscript submitted), and (iii) the ability of Bin1 to complement defects in stressinduced cell cycle control that are generated in fission yeast following deletion of the Bin1 homolog hob1+ (Routhier et al, 2003). In summary, Bin1 adapter proteins have complex signaling functions in animal cells, perhaps related to stress signaling, that have yet to be fully understood.…”

“…Notably, isoforms of Bin1 that localize to the nucleus can suppress transformation by Myc and other oncogenes, and trigger p53-independent apoptosis in human breast cancers, prostate cancers, melanomas, astrocytomas, and neuroblastomas where expression of the endogenous Bin1 gene is frequently lost, altered, or inactivated (Sakamuro et al, 1996;Elliott et al, 1999Elliott et al, , 2000Galderisi et al, 1999;Ge et al, 1999Ge et al, , 2000aHogarty et al, 2000;Huang et al, 2000). A recent study of the Bin1 homolog in fission yeast, hob1+, identifies an evolutionarily conserved requirement in stress-signaling and cell cycle control (Routhier et al, 2003). We have proposed that Bin1 adapter proteins act as 'bridging integrators' that link nuclear and cytosolic stress-signaling pathways in cells, perhaps coupling nuclear regulators such as c-Myc to actin control or vesicle dynamics (Prendergast, 1999).…”

Targeted deletion of the suppressor gene bin1/amphiphysin2 accentuates the neoplastic character of transformed mouse fibroblasts

“…Amphiphysin2) associate with endocytotic complexes, however, gene knockout studies in mouse, Drosophila, and fission yeast indicate that Bin1 is nonessential for endocytosis. 16,[19][20][21] Instead, recent studies suggest that this association may reflect some role in trafficking processes. 22,23 In yeast, genetic studies of the conserved BAR adapter proteins (homologs of mammalian Bin1/Amphiphysin2 and Bin3) highlight connections to actin control and stress signaling.…”