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 Gbetagamma dimer; downstream effectors for its alpha subunit (Goalpha) have not been clearly defined. Here, we employ the yeast two-hybrid system to screen for Goalpha-interacting partners in a cDNA library from human fetal brain. The transcription factor promyelocytic leukemia zinc finger protein (PLZF) specifically bound to Goalpha. Interactions between PLZF and Goalpha were confirmed using in vitro and in vivo affinity binding assays. Activated Goalpha interacted directly with PLZF, and enhanced its function as a transcriptional and cell growth suppressor. Notably, PLZF activity was additionally promoted by the Go/ialpha-coupled cannabinoid receptor (CB) in HL60 cells endogenously expressing CB and PLZF. These results collectively suggest that Goalpha modulates the function of PLZF via direct interactions. Our novel findings provide insights into the diverse cellular roles of Goalpha and its coupled receptor.
Won
Jung Hee
JH
Department of Life Science, Kyonggi University, Suwon 443-760, South Korea.
Park
Jung Sik
JS
Ju
Hyun Hee
HH
Kim
Soyeon
S
Suh-Kim
Haeyoung
H
Ghil
Sung Ho
SH
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D066298:In Vitro Techniques; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011485:Protein Binding; D043882:Receptors, Cannabinoid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
D017931:DNA Primers; D051741:Kruppel-Like Transcription Factors; D046912:Multiprotein Complexes; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D043882:Receptors, Cannabinoid; D011993:Recombinant Fusion Proteins; C092037:ZBTB16 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go