5581

PRKCE

PKCE|nPKC-epsilon;protein kinase C, epsilon;PRKCE;protein kinase C, epsilon

protein kinase C epsilon type

2p21

protein-coding

BACKGROUND: Since the end of last century, RNAs from the 3untranslated region (3UTR) of several eukaryotic mRNAs have been found to exert tumor suppression activity when introduced into malignant cells independent of their whole mRNAs. In this study, we sought to determine the molecular mechanism of the tumor suppression activity of a short RNA from 3UTR of C/EBPbeta mRNuAlpha (C/EBPbeta 3UTR RNA) in human hepatocarcinoma cells SMMC-7721. METHODOLOGY/PRINCIPAL FINDINGS: By using Western blotting, immunocytochemistry, molecular beacon, confocal microscopy, protein kinase inhibitors and in vitro kinase assays, we found that, in the C/EBPbeta 3UTR-transfectant cells of SMMC-7721, the overexpressed C/EBPbeta 3UTR RNA induced reorganization of keratin 18 by binding to this keratin; that the C/EBPbeta 3UTR RNA also reduced phosphorylation and expression of keratin 18; and that the enzyme responsible for phosphorylating keratin 18 is protein kinase Cepsilon. We then found that the C/EBPbeta 3UTR RNA directly inhibited the phosphorylating activity of protein kinase Cepsilon; and that C/EBPbeta 3UTR RNA specifically bound with the protein kinase Cepsilon-keratin 18 conjugate. CONCLUSION/SIGNIFICANCE: Together, these facts suggest that the tumor suppression in SMMC-7721 by C/EBPbeta 3UTR RNA is due to the inhibition of protein kinase Cepsilon activity through direct physical interaction between C/EBPbeta 3UTR RNA and protein kinase Cepsilon. These facts indicate that the 3UTR of some eukaryotic mRNAs may function as regulators for genes other than their own.