Identification of endogenous substrates for HRASLS family members and their functional analysis

我们研究了最初被确定为肿瘤抑制基因的HRASLS家族成员可能的脂质代谢活性。我们发现所有的HRASLS家族成员都具有以甘油磷脂为底物的脂质代谢活性。因此，我们将HRASLS1-5基因的产物分别命名为磷脂酶A/酰基转移酶(PLA/ AT)-1-5。为了分析PLA/ AT-3在活细胞中的生物学功能，我们制备了稳定表达PLA/ AT-3的HEK293细胞。细胞检查显示过氧化物酶体功能障碍和醚型脂质水平急剧下降引起的过氧化物酶体功能障碍。结果表明，PLA/ AT-3通过磷脂代谢酶的作用调节细胞内过氧化物酶体的含量。

We investigated possible lipid-metabolizing activities of HRASLS family members which were originally identified as tumor suppressor genes. We found that all of HRASLS family members possess lipid-metabolizing activities using glycerophospholipids as substrate. Thus, we termed the products of HRASLS1-5 genes as phospholipase A/ acyltransferase(PLA/ AT)-1-5, respectively. To analyze the biological functions of PLA/ AT-3 in living cells, we generated HEK293 cells stably expressing PLA/ AT-3. The examination of the cells revealed dysfunction of peroxisomes and a drastic decrease in the levels of ether-type lipids caused by the peroxisomal dysfunction. The results suggest that PLA/ AT-3 regulates intracellular content of peroxisomes by functioning as a phospholipid-metabolizing enzyme.