title: Characterization of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes.
abstract: Tazarotene-induced protein 3 (TIG3) and HRAS-like suppressor family 2 (HRASLS2) exhibit tumor-suppressing activities and belong to the lecithin retinol acyltransferase (LRAT) protein family. Since Ca(2+)-independent N-acyltransferase and H-rev107 (another tumor suppressor), both of which are members of the LRAT family, have been recently reported to possess catalytic activities related to phospholipid metabolism, we examined possible enzyme activities of human TIG3 and HRASLS2 together with human H-rev107. The purified recombinant proteins of TIG3, HRASLS2, and H-rev107 functioned as phospholipase (PL) A(1/2) in a Ca(2+)-independent manner with maximal activities of 0.53, 0.67, and 2.57 micromol/min/mg of protein, respectively. The proteins were active with various phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), and for most of substrates the PLA(1) activity was much higher than the PLA(2) activity. In addition, HRASLS2 catalyzed N-acylation of PE to form N-acyl-PE and O-acylation of lyso PC to form PC. TIG3 and H-rev107 catalyzed the N-acylation and O-acylation at relatively low rates. Moreover, these three proteins showed different expression profiles in human tissues. These results suggest that the tumor suppressors TIG3, HRASLS2 and H-rev107 are involved in the phospholipid metabolism with different physiological roles.
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: Xing-Hua
authors.initials: XH
authors.lastname: Jin
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Takeharu
authors.initials: T
authors.lastname: Tonai
authors.forename: Natsuo
authors.initials: N
authors.lastname: Ueda
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D055162:Biocatalysis; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010714:Phosphatidylethanolamines / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D054512:Phospholipases A2, Calcium-Independent; D010743:Phospholipids / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008244:Lysophosphatidylcholines; C437968:PLAAT4 protein, human; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; C483858:phosphatidylethanolamine; C530743:PLAAT2 protein, human; C490065:PLAAT3 protein, human; D054467:Phospholipases A2; D054512:Phospholipases A2, Calcium-Independent