The alpha subunit of Go interacts with promyelocytic leukemia zinc finger protein and modulates its functions

Heterotrimeric GTP-binding proteins (G proteins) mediate signal transduction generated by neurotransmitters and hormones. Go, a member of the Go/Gi family, is the most abundant heterotrimeric G protein in the brain. Most mechanistic analyses on Go activation demonstrate that its action is mediated by the Gβγ dimer; downstream effectors for its α subunit (Goα) have not been clearly defined. Here, we employ the yeast two-hybrid system to screen for Goα-interacting partners in a cDNA library from human fetal brain. The transcription factor promyelocytic leukemia zinc finger protein (PLZF) specifically bound to Goα. Interactions between PLZF and Goα were confirmed using in vitro and in vivo affinity binding assays. Activated Goα interacted directly with PLZF, and enhanced its function as a transcriptional and cell growth suppressor. Notably, PLZF activity was additionally promoted by the Go/iα-coupled cannabinoid receptor (CB) in HL60 cells endogenously expressing CB and PLZF. These results collectively suggest that Goα modulates the function of PLZF via direct interactions. Our novel findings provide insights into the diverse cellular roles of Goα and its coupled receptor.