| First Author | Liu X | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 36 |
| Issue | 3 | Pages | 421-37 |
| PubMed ID | 26598603 | Mgi Jnum | J:235990 |
| Mgi Id | MGI:5804085 | Doi | 10.1128/MCB.00510-15 |
| Citation | Liu X, et al. (2015) Natural Functions of PLIN2 Mediating Wnt/LiCl Signaling and Glycogen Synthase Kinase 3 (GSK3)/GSK3 Substrate-Related Effects Are Modulated by Lipid. Mol Cell Biol 36(3):421-37 |
| abstractText | Belonging to the PLIN family, PLIN2 associates with lipid storage droplets (LSDs), but other functions of PLIN2 remain unclear. Here, we suggest that PLIN2 mediates Wnt signaling because PLIN2 small interfering RNA (siRNA) suppresses activation of Wnt/coreceptor pathways. The mediation in the Wnt/Frizzled pathway seems to occur from Dishevelleds to axin/glycogen synthase kinase 3(GSK3)/beta-catenin complexes (AGbetaC) as Wnt decreases Dishevelled/PLIN2 but increases AGbetaC/PLIN2 associations. Augmenting cellular LSDs that affect PLIN2 associations with these proteins, oleic acid (OA) treatment inhibits Wnt-increased AGbetaC/PLIN2 associations and beta-catenin T-cell factor signaling (beta-CTS). Revealing that PLIN2 is a GSK3-associated protein, the study explored PLIN2-mediated effects on GSK3/GSK3 substrates. PLIN2 siRNA reduces inhibitory GSK3 levels and lithium chloride (LiCl)-upregulated beta-catenin or CCAAT/enhancer binding protein alpha (c/EBPalpha) expression. OA treatment decreases LiCl-increased c/EBPalpha via PLIN2-c/EBPalpha dissociation. In addition to PLIN2 overexpression increasing beta-CTS, PLIN2 depletion or overexpression drops or adds expression of GSK3 substrates, such as beta-catenin, c/EBPalpha,c-Myc, cyclin D1, and insulin receptor substrate 1, and cell growth/survival. PLIN2 N or C terminus overexpression that is associated with higher levels of the substrates suggests that those substrates bind to specific regions of PLIN2. Mimicking the possible high lipid concentrations in cells in the human body under conditions of hyperlipidemia/obesity, OA-treated cells gain or reduce GSK3 substrate expression in parallel with a decrease (a Wnt-like effect) or increase in GSK3 activity, likely regulated by GSK3/PLIN2/GSK3 substrate associations. |
