Abstract
H-rev107 is a member of the HREV107 type II tumor suppressor gene family and acts as a phospholipase to catalyze the release of fatty acids from glycerophospholipid. H-rev107 has been shown to play an important role in fat metabolism in adipocytes through the PGE2/cAMP pathway, but the detailed molecular mechanism underlying H-rev107-mediated lipid degradation has not been studied. In this study, the interaction between H-rev107 and cytochrome P450 reductase (POR), which is involved in hepatic lipid content regulation, was determined by yeast two-hybrid screen and confirmed by using in vitro pull down assays and immunofluorescent staining. The expression of POR in H-rev107-expressing cells enhanced the H-rev107-mediated release of arachidonic acid. However, H-rev107 inhibited POR activity and relieved POR-mediated decreased triglyceride content in HtTA and HeLa cervical cells. The inhibitory effect of H-rev107 will be abolished when POR-expressing cells transfected with PLA2-lacking pH-rev107 or treated with PLA2 inhibitor. Silencing of H-rev107 using siRNA resulted in increased glycerol production and reversion of free fatty acid-mediated growth suppression in Huh7 hepatic cells. In summary, our results revealed that H-rev107 is also involved in lipid accumulation in liver cells through the POR pathway via its PLA2 activity.
Highlights
H-rev107 was identified in H-RAS-resistant murine fibroblasts [1] and has been identified as HRASLS3 [2] and PLA2G16 [3]
H-rev107 is encoded by a 3.5-kb mRNAthat can be translated to a 17.9-kDa protein that belongs to the HREV107 protein family, which includes HREV107 [4], retinoid-inducible gene 1 (RIG1) [5], HRASLS2 [6], HRLP5 [7], and HRASLS [8]
This study suggests that H-rev107 plays an important role in fat metabolism, which may contribute to the regulation of cellular differentiation in both normal and cancer cells
Summary
H-rev107 was identified in H-RAS-resistant murine fibroblasts [1] and has been identified as HRASLS3 [2] and PLA2G16 [3]. HREV107 family proteins play important roles in the regulation of cellular growth, differentiation, and apoptosis [11,12,13,14,15,16,17]. This study suggests that H-rev107 plays an important role in fat metabolism, which may contribute to the regulation of cellular differentiation in both normal and cancer cells. The proline-rich region binds to protein phosphatase 2A and inhibits the enzyme's activity [2] Both the proline-rich region and the C-terminal transmembrane domain play important roles in H-rev107-mediated down-regulation of peroxisomes through binding to Pex and inhibiting its chaperone activity [26]. We demonstrated a role for H-rev107 in lipid accumulation in liver cells through the POR pathway via its PLA2 activity
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