The 2004 Nobel Prize in Chemistry was awarded to Aaron Chiechanover, Avram Hershko and Irwin Rose for their pioneering studies of ubiquitination and its role in regulating protein stability. Now, 30 years after their discovery, we are beginning to understand the pleiotropic nature of ubiquitin and its roles in diverse physiological processes. Here we review an emerging concept that the signal ling pathways that control inflammation are tightly regulated by a multitude of ubiquitination and deubiquitination reactions.

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