The ‘canonical’ hallmark of the proteasomal recognition signal is a polyubiquitin chain. Recently, it has become clear that the signal is far more complex and diverse, and contains information derived from both ubiquitin and the substrate. Thus, the proteasome can recognize substrates modified by a single (monoubiquitination) or several single (multiple monoubiquitinations) ubiquitins, short chains (oligoubiquitination), and possibly also long chains (polyubiquitination). We have recently shown that the p105 NF-B precursor is processed to the p50 active subunit of the transcriptional regulator following multiple monoubiquitination, and that this process is probably mediated by the KPC1 ubiquitin ligase. Overexpression of the ligase with excessive generation of p50 results in strong tumor suppression.
