Study shows that Cullin-RING Ligase-2 (CRL2) activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Synergising cryo-electron microscopy with mass spectrometry study identified sensory regions of the COP9 signalosome that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members.
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