Cell-division inhibitors: new insights for future antibiotics.

The growing problem of antibiotic resistance has been exacerbated by the use of new drugs that are merely variants of older overused antibiotics. While it is naive to expect to restrain the spread of resistance without controlling antibacterial usage, the desperate need for drugs with novel targets has been recognized by health organizations, industry and academia alike. The wealth of knowledge available about the bacterial cell-division pathway has aided target-driven approaches to identify novel inhibitors.

Preparation of monoclonal antibodies against the spindle checkpoint kinase Bub1.

The Bub1 kinase is a critical component of the spindle checkpoint involved in monitoring the separation of sister chromatids at mitosis. The viral oncoprotein Simian virus 40 large T antigen (LT) can bind and perturb the spindle checkpoint function of Bub1. We have developed three highly specific monoclonal antibodies against the Bub1 protein and have demonstrated that they can all detect Bub1 via Western blotting and immunofluorescence, in addition to their ability to immunoprecipitate Bub1.

Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1.

The mitotic spindle checkpoint protein Bub1 has been found to be mutated at low frequency in certain human cancers characterized by aneuploidy. Simian virus 40 large T antigen efficiently immortalizes rodent cells and occasionally transforms them to tumorigenicity. T antigen can also cause genomic instability, inducing chromosomal aberrations and aneuploidy.