Left: The gene SF3B1 encodes a protein (maroon) that is part of the SF3b complex (multiple colors), which is part of the spliceosome (not shown). Right: A significant number of cancer cells contain just one copy of SF3B1, rather than two, which leads to a reduced abundance of the SF3b complex in cells. Such cells are sensitive to further loss of SF3B1 through genetic down-regulation (top) or ubiquitination by a ligase (bottom). Cancer cells employ deubiquitinases to reverse the effects of ubiquitination, so drugs that inhibit these deubiquitinases could be used to treat some cancers. CYCLOPS: copy-number alterations yielding cancer liabilities owing to partial loss; DUBi: deubiquitinase inhibitor.