PDZ domains contain approximately 90 amino acids and bind the extreme C terminus of proteins in a sequence-specific manner. PIST, a PDZ domain-containing Golgi protein, was discovered in a yeast two-hybrid system as a binding partner to Beclin-1, a Bcl-2-interacting protein homologous to the yeast autophagy gene apg6. Experiments with mutant PIST proteins lacking the PDZ domain showed that PIST interaction with Beclin-1 through its coiled-coil domain can modulate Beclin-1 activity and suggest that PIST interactions with other proteins through its PDZ domain may regulate the activity of PIST and Beclin-1.