Abstract
The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. Although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. Encoded in operons, these components are likely representative of the progenitor apparatus that founded the modern eukaryotic ubiquitin modification systems. Here we report that these proteins from the archaeon Candidatus ‘Caldiarchaeum subterraneum’ operate together as a bona fide ubiquitin modification system, mediating a sequential ubiquitylation cascade reminiscent of the eukaryotic process. Our observations support the hypothesis that complex eukaryotic ubiquitylation signalling pathways have developed from compact systems originally inherited from an archaeal ancestor.
Highlights
The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions
We reveal that the C. subterraneum genome does encode a fully functional and minimal ubiquitylation system
Having revealed that the C. subterraneum E1/E2/E3 cascade does appear to operate in a manner reminiscent of the eukaryotic ubiquitylation systems, potentially forming covalently linked ubiquitin chains extending from substrates, we examined if the Rpn11/JAMM metalloprotease homologue, encoded in the genome close to the ubiquitin operon, could deconjugate these isopeptide linkages
Summary
The covalent modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions. It is well documented that the attachment of the ubiquitin small modifier is central to proteasomal degradation pathways, transcriptional control, DNA repair, cell cycle regulation and a plethora of other regulatory pathways[1,2,3,4,5,6,7,8]. How these ubiquitylation systems were acquired by the earliest eukaryotes and subsequently developed into the sophisticated apparatus employed by the most complex descendants has garnered considerable interest of late.
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