title: Regulation of peroxisomal lipid metabolism by catalytic activity of tumor suppressor H-rev107.
abstract: H-rev107 is a mammalian protein belonging to the HRAS-like suppressor family. Although the protein was originally found as a tumor suppressor, currently it is receiving considerable attention as a regulator of adipocyte lipolysis. We recently revealed that purified recombinant H-rev107 has phospholipase A(1/2) activity, releasing free fatty acids from glycerophospholipids with a preference for esterolysis at the sn-1 position. In the present study, we constitutively expressed H-rev107 in cloned HEK293 cells to examine its biological function in living cells. Initially, the cells accumulated free fatty acids. We also found a remarkable decrease in the levels of ether-type lipids, including plasmalogen and ether-type triglyceride, with a concomitant increase in fatty alcohols, substrates for the biosynthesis of ether-type lipids. Considering that peroxisomes are involved in the ether-type lipid biosynthesis, we next focused on peroxisomes and found that the peroxisomal markers 70-kDa peroxisomal membrane protein and catalase were abnormally distributed in the transfected cells. These biochemical and morphological abnormalities were not seen in HEK293 cells stably expressing a catalytically inactive mutant of H-rev107. When H-rev107 or its fusion protein with enhanced green fluorescence protein was transiently expressed in mammalian cells, both proteins were associated with peroxisomes in some of the observed cells. These results suggest that H-rev107 interferes with the biosynthesis of ether-type lipids and is responsible for the dysfunction of peroxisomes in H-rev107-expressing cells.
authors.affiliation: Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Uyama
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ichi
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Jin
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Araki
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Natsuo
authors.initials: N
authors.lastname: Ueda
mesh_terms: D000818:Animals; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D020675:Peroxisomes / Q000201:enzymology* / Q000235:genetics; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008055:Lipids; D025521:Tumor Suppressor Proteins; D054512:Phospholipases A2, Calcium-Independent; C490066:Plaat3 protein, mouse