In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 5276-5276
Abstract:
H-rev107, also called HRASLS3 or PLA2G16, is a member of the HREV107 type II tumor suppressor gene family that includes HREV107, Retinoid-inducible gene 1, and HRASLS. The HREV107 protein family contains an NC domain, with unknown function at the N-terminus, and a hydrophobic membrane-anchoring domain at the C-terminus. Previous study showed that the H-rev107 gene specifically expressed in H-ras resistant fibroblasts. However, the mode of action and the site of inhibition of H-rev107 are still unknown. Our results revealed that H-rev107 reduced the levels of activated RAS (RAS-GTP) or Elk1-mediated transactivation in epidermal growth factor stimulated HtTA cells that expressed H-RAS. Further, we found that H-rev107 reduced H-RAS palmitoylation determined by acyl-biotin exchange assay. Palmitoylation or S-acylation is the post-translational attachment of fatty acids to cysteine residues and continuous cycles of de- and reacylation reactions accounts for the specific subcellular distribution of RAS. H-rev107 was shown as a phospholipase A/Acyltransferase (PLA/AT) that involved in the phospholipid metabolism. We next determined whether H-rev107 affected H-RAS palmitoylation through deacylation/acylation by acyl-protein thioesterases (APT1) or PLA/AT using APT1 inhibitor (palmostatin B) or PLA/AT inhibitor (arachidonyl trifluoromethyl ketone, AACOCF3). Treating cells with AACOCF3 can increase H-rev107-induced acylated H-RAS suppression of HtTA cells. Also, AACOCF3 significantly increased the levels of activated RAS and Elk-mediated transactivation in H-rev107 expressed cells. However, treating cells with palmostatin B enhanced H-rev107-induced acylated H-RAS suppression in H-rev107 expressing cells. In conclusion, H-rev107 can inhibit H-RAS palmitoylation to reduce its GTP-form levels and further suppress the downstream signal pathway. Our study suggested that PLA/AT activity of H-rev107 might play an important role in H-rev107 mediated RAS suppression. Note: This abstract was not presented at the meeting. Citation Format: Fu-Ming Tsai, Chang-Chieh Wu, Chun-Hua Wang, Tzung-Chieh Tsai, Rong-Yaun Shyu, Shun-Yuan Jiang. Phospholipase A/acyltransferase enzyme activity of H-rev107 inhibits the H-RAS signal pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5276. doi:10.1158/1538-7445.AM2014-5276
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-5276
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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