Characterization of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes

Toru Uyama; Xing-Hua Jin; Kazuhito Tsuboi; Takeharu Tonai; Natsuo Ueda

doi:10.1016/j.bbalip.2009.07.001

Characterization of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes

Biochim Biophys Acta. 2009 Dec;1791(12):1114-24. doi: 10.1016/j.bbalip.2009.07.001. Epub 2009 Jul 14.

Authors

Toru Uyama¹, Xing-Hua Jin, Kazuhito Tsuboi, Takeharu Tonai, Natsuo Ueda

Affiliation

¹ Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.

PMID: 19615464
DOI: 10.1016/j.bbalip.2009.07.001

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acylation
Amino Acid Sequence
Animals
Biocatalysis
COS Cells
Cell Line, Tumor
Chlorocebus aethiops
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genome, Human / genetics
Humans
Intracellular Signaling Peptides and Proteins / chemistry
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / isolation & purification
Intracellular Signaling Peptides and Proteins / metabolism
Lysophosphatidylcholines / metabolism
Models, Biological
Molecular Sequence Data
Phosphatidylethanolamines / metabolism
Phospholipases A2 / metabolism
Phospholipases A2, Calcium-Independent
Phospholipids / metabolism*
Receptors, Retinoic Acid / chemistry
Receptors, Retinoic Acid / genetics
Receptors, Retinoic Acid / isolation & purification
Receptors, Retinoic Acid / metabolism*
Recombinant Proteins / metabolism
Stereoisomerism
Substrate Specificity
Tumor Suppressor Proteins / chemistry
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / isolation & purification
Tumor Suppressor Proteins / metabolism*

Substances

Intracellular Signaling Peptides and Proteins
Lysophosphatidylcholines
PLAAT4 protein, human
Phosphatidylethanolamines
Phospholipids
Receptors, Retinoic Acid
Recombinant Proteins
Tumor Suppressor Proteins
phosphatidylethanolamine
PLAAT2 protein, human
PLAAT3 protein, human
Phospholipases A2
Phospholipases A2, Calcium-Independent