FAM83G Is a Novel Inducer of Apoptosis

The family with sequence similarity 83 (FAM83) protein family G (FAM83G) possesses a predicted consensus phosphorylation motif for serine/threonine-protein kinase D1/protein kinase C mu (PKD1/PKC mu) at serine residue 356 (S356). In this study, overexpressed wild-type FAM83G coimmunoprecipitated with PKD1/PKC mu in Chinese hamster ovary (CHO) cells inhibited heat shock protein 27 (HSP27) phosphorylation at S82 and reduced the living cell number. The expression of a FAM83G phosphorylation-resistant mutant (S356A-FAM83G) had no effect on the living cell number or the induction of spontaneous apoptosis. By contrast, the introduction of a synthetic peptide encompassing FAM83G S356 into HCT116 and HepG2 cells decreased HSP27 S15 and S82 phosphorylation and induced spontaneous apoptosis. On the other hand, the introduction of FAM83G phosphorylation-resistant mutant synthesized peptides (S356A-AF-956 and S356A-AG-066) did not reduce the living cell number or induce spontaneous apoptosis. The endogenous expression of HSP27 and FAM83G was apparently greater in HCT116 and HepG2 cells compared with in CHO cells. In various types of lung cancer cell lines, the FAM83G messenger RNA (mRNA) level in non-small lung cancer cells was at a similar level to that in non-cancerous cells. However, the FAM83G mRNA level in the small cell lung cancer cell lines was variable, and the HSP27 mRNA level in FAM83G mRNA-rich types was greater than that in FAM83G mRNA-normal range types. Taken together, these data demonstrate that FAM83G S356 phosphorylation modulates HSP27 phosphorylation and apoptosis regulation and that HSP27 is a counterpart of FAM83G.