Construction of polyubiquitin chain specific molecular probes and their applications to histopathologic examinations.

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The ubiquitin system functions as a pivotal post-transcriptional modification in numerous cellular functions, including protein degradation and signal transduction. We identified that LUBAC (linear ubiquitin chain assembly complex) generates a novel type of Met1-linked linear polyubiquitin chain and specifically regulates the NF-κB pathway, which is a central signaling pathway for inflammatory and immune responses. In this study, we show that A20, a deubiquitinase, suppresses NF-κB activation by binding linear polyubiquitin via the C-terminal seventh zinc finger (ZF7), and we determined the crystal structures of A20 ZF7 in complex with linear diubiquitin. Importantly, we found that a tandem conjugate of three ZF7s is available as a high affinity molecular probe to detect linear poluubiquitin chain.