G protein γ subunit 7 induces autophagy and inhibits cell division.

Juanjuan Liu,Xingxing Yang,Zhiyuan Li,Xinmiao Ji,Wenchao Wang,Xin Zhang

doi:10.18632/oncotarget.8559

Abstract

GNG7 (G protein γ subunit 7), a subunit of heterotrimeric G protein, is ubiquitously expressed in multiple tissues but is down-regulated in various cancers. Its expression could reduce tumor volume in mice but the mechanism was not clear. Here we show that GNG7 overexpression inhibits cell proliferation and increases cell death. GNG7 level is cell cycle-dependent and it regulates actin cytoskeleton and cell division. In addition, GNG7 is an autophagy inducer, which is the first reported Gγ protein involved in autophagy. GNG7 knockdown reduces Rapamycin and starvation-induced autophagy. Further analysis reveals that GNG7 inhibits MTOR in cells, a central regulator for autophagy and cell proliferation. In conclusion, GNG7 inhibits MTOR pathway to induce autophagy and cell death, inhibits cell division by regulating actin cytoskeleton. These combined effects lead to the antitumor capacity of GNG7.

Highlights

Heterotrimeric G proteins are activated by upstream receptors and their specific interactions are the major factors governing the differential functions of the large numbers of GPCRs (G protein coupled receptors)
We found that GNG7 knockdown efficiently reduced BAF-induced LC3BII/I increase from 2.6 fold to 1.4 fold (p < 0.05) (Figure 6E and Figure 6F), which suggests that GNG7 knockdown decreases the autophagy flux in cells
GNG7 is the first reported Gγ protein that functions in autophagy

Summary

Introduction

Heterotrimeric G proteins are activated by upstream receptors and their specific interactions are the major factors governing the differential functions of the large numbers of GPCRs (G protein coupled receptors). G proteins are the major effectors of GPCRs at the cell membrane, mounting evidences suggest that G proteins have additional functions other than the traditional GPCR binding partners. It has been well established that the Gβγ works as a dimer, some reports show that Gβ or Gγ subunits interact with a number of novel binding partners having special domains and are functionally distinct from conventional Gβγ dimers [14,15,16], indicating that they have independent roles

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Results

Conclusion