PHOSDUCIN-LIKE PROTEIN (PHLP), A REGULATOR OF G-BETA-GAMMA FUNCTION, INTERACTS WITH THE PROTEASOMAL PROTEIN SUG1

Phosducin-like protein (PhLP) and phosducin are highly homologous prot eins that interact with the beta gamma subunits of guanine nucleotide binding proteins. While phosducin has a well-characterized role in ret inal signal transduction, PhLP function remains unclear. To further un derstand the function of PhLP, we have examined other potential protei n:protein interactions with PhLP using the yeast two-hybrid system. Ph LP was found to interact with a mouse homologue of the yeast SUG1, a s ubunit of the 26S proteasome which may also indirectly modulate transc ription, This interaction was further confirmed by an in vitro binding assay and co-immunoprecipitation of the two proteins in overexpressio n studies. Inhibition of proteasome function by lactacystin led to acc umulation of high molecular weight, ubiquitin-immunoreactive protein p recipitated by PhLP antiserum. We suggest that PhLP/SUG1 interaction m ay target PhLP for proteasomal degradation. (C) 1998 Elsevier Science B.V.