Murphy et al. describe a novel pseudokinase architecture from human TRIB1 and characterize its substrate-recognition motif within the C/EBPα transcription factor. Combined with biophysical studies, this shows how Tribbles proteins eschew catalytic activity in favor of function as signaling scaffolds.
Protein Trib1 plays a vital role in controlling how and when other proteins are degraded, which is essential for managing protein levels in the cell. The finding could be used to develop new drugs to treat cancers such as leukaemia, caused by malfunctioning of the Trib1 protein.
Trib1 is part of the protein family Tribbles, which play diverse roles in cell signalling and development. Tribbles are named after the small, furry creatures from Star Trek that reproduce uncontrollably...
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