Indisulam is an aryl sulfonamide drug with selective anticancer activity. Its mechanism of action and the basis for its selectivity have so far been unknown. Here we show that indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation. Mutations in RBM39 that prevent its recruitment to CUL4-DCAF15 increase RBM39 stability and confer resistance to indisulam's cytotoxicity. RBM39 associates with precursor messenger RNA (pre-mRNA) splicing factors, and inactivation of RBM39 by indisulam causes aberrant pre-mRNA splicing. Many cancer cell lines derived from hematopoietic and lymphoid lineages are sensitive to indisulam, and their sensitivity correlates with DCAF15 expression levels. Two other clinically tested sulfonamides, tasisulam and chloroquinoxaline sulfonamide, share the same mechanism of action as indisulam. We propose that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs (splicing inhibitor sulfonamides).

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Gaskill's essay situates Stephen Crane's well-known fascination with color within the historical and philosophical contexts of the late-nineteenth century. The invention of bright synthetic dyes and pigments and their applications within emerging advertising culture combined with theories of color sensation and perception offered by empirical psychologists to produce new opportunities for and understandings of color experience. Color—increasingly puzzled over in the abstract, apart from any instantiations within objects—came to be regarded as an affective force with direct and controllable effects on human minds and bodies. In stories such as “The Blue Hotel” and “The Broken-Down Van” and in the novels The Red Badge of Courage and The Third Violet, Crane draws from and contributes to these experiments with abstract or “pure” color. He uses color to explore the networks of sensation, perception, and language that constitute experience, and he develops a literary style that lifts the feeling of colors from their visual appearances in order to bring his language into contact with the sensory and affective force of color. In this regard, Crane's color techniques relate to late-nineteenth-century philosophical discussions of qualia. This essay elaborates on these themes and practices—touching on Goethe's Theory of Colours, Art Nouveau, the work of Charles Sanders Peirce, and chromotherapy—to offer an account of Crane's colors that revises critical accounts of his “impressionism” and that attends to historical understandings of the character of experience.