A proinflammatory cytokine inhibits p53 tumor suppressor activity

p53 has a key role in the negative regulation of cell proliferation, in the maintenance of genomic stability, and in the suppression of transformation and tumorigenesis. To identify novel regulators of p53, we undertook two f unctional screens to isolate genes which bypassed either p53-mediated growt h arrest or apoptosis. In both screens, we isolated cDNAs encoding macropha ge migration inhibitory factor (MIF), a cytokine that was shown previously to exert both local and systemic proinflammatory activities. Treatment with MIF overcame p53 activity in three different biological assays, and suppre ssed its activity as a transcriptional activator. The observation that a pr oinflammatory cytokine. MIF, is capable of functionally inactivating a tumo r suppressor, p53, may provide a link between inflammation and tumorigenesi s.