FAM83G Is a Novel Inducer of Apoptosis.

Junichi Okada,Eijiro Yamada,Jeffrey E Pessin,Shuichi Okada,Tsugumichi Saito,Kazuya Okada,Masanobu Yamada,Yasuyo Nakajima,Atsushi Ozawa,Noriaki Sunaga

doi:10.3390/molecules25122810

Junichi Okada, Eijiro Yamada + Show 8 more

Open Access

https://doi.org/10.3390/molecules25122810

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Abstract

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/PKCμ) at serine residue 356 (S356). In this study, overexpressed wild-type FAM83G coimmunoprecipitated with PKD1/PKCμ 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.

Highlights

The family with sequence similarity 83 (FAM83) protein family comprises eight known members: FAM83A–FAM83H [1,2]
We found that endogenous FAM83G protein was co-immunoprecipitated with endogenous PKD1/PKCμ, as shown in the pCMV6 lane
On the other hand, overexpressed FAM83G was co-immunoprecipitated with an increased amount of PKD1/PKCμ compared to that of pCMV6 samples as shown in the pCMV6-wild-type (WT)-FAM83G lane

Summary

Introduction

The family with sequence similarity 83 (FAM83) protein family comprises eight known members: FAM83A–FAM83H [1,2]. Members of the FAM83 family share a conserved N terminal domain of approximately 300 amino acids (Pfam DUF1669 domain), which is homologous to the phospholipase. Owing to the absence of essential catalytic histidine residues, this domain is unlikely to have phospholipase activity [3,4]. FAM83G likely has a unique physiological function among the FAM83 protein family members. FAM83G has been reported to play a key role in palmoplantar keratoderma [1,2,4]. It has not yet been reported whether

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