The hPLIC proteins may provide a link between the ubiquitination machineryand the proteasome

Although there is a binding site on the proteasome for the polyubiquitin ch ains attached to degradation substrates by the ubiquitination machinery, it is currently unclear whether in vivo the activities of the ubiquitination machinery and the proteasome are coupled. Here we shaw that two human homol ogs of the yeast ubiquitin-like Dsk2 protein, hPLIC-1 and hPLIC-2, physical ly associate with both proteasomes and ubiquitin ligases in large complexes . Overexpression of hPLIC proteins interferes with the in vivo degradation of two unrelated ubiquitin-dependent proteasome substrates, p53 and I kappa B alpha, but not a ubiquitin-independent substrate. Our findings raise the possibility that the hPLIC proteins, and possibly related ubiquitin-like f amily members, may functionally link the ubiquitination machinery to the pr oteasome to affect in vivo protein degradation.