The selective HDAC6 inhibitor, tubacin, is pictured superimposed over A549 lung adenocarcinoma cells treated with bortezomib. Proteasome inhibition induces polyubiquitinated protein stress and the formation of aggresomes, imaged with anti-ubiquitin immunofluorescence and false-colored green. Aggresome formation requires the catalytic activity of HDAC6, identifying a rational approach to combination chemotherapy using combined proteasome and aggresome inhibition. Tubacin is one of many diversity-oriented synthesis molecules that are synthesized and made available for screening at the National Cancer Institute’s Initiative for Chemical Genetics. Photo and structure courtesy of Drs. James E. Bradner and Ralph Mazitschek. For details, see the article by Tolliday et al. on page 8935 of this issue.

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