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Regulation of Ras localization and cell transformation by evolutionarily conserved palmitoyltransferases (950.5)
Author(s) -
Young Evelin,
Zheng ZeYi,
Wilkins Angela,
Jeong HeeTae,
Min Li,
Lichtarge Olivier,
Chang Eric
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.950.5
Subject(s) - microbiology and biotechnology , golgi apparatus , biology , gtpase , cytoplasm , mutagenesis , mutant , gene , genetics , endoplasmic reticulum
Ras GTPases act on the plasma membrane (PM) to mediate signaling that can lead to tumorigenesis. Ras trafficking to the PM is influenced by a series of post‐translational modifications of the Ras C‐terminus, however the identity and necessity of the regulatory proteins are not clear. In an effort to find proteins that are necessary for Ras trafficking to the PM, we conducted an unbiased genomic mutagenesis screen in fission yeast where we sought mutants with diminished PM Ras. Only 5 mutants were found, all defective in the same gene, sp‐erf2, creating sp‐Erf2p, with varying activities. Sp‐Erf2p is a DHHC protein acyl transferase (DHHC‐PAT) functioning at the Golgi for efficient Ras palmitoylation. Sp‐Erf2p is one of five fission yeast DHHC‐PATs and it is closely related to human zDHHC9, previously shown as a Ras PAT in vitro. We show that zDHHC9 efficiently rescued sp‐erf2 null phenotypes and, when repressed in mammalian cells, N/H‐Ras became diminished at the PM and mislocalized into the cytoplasm, and Ras‐induced transformation is reduced. These data illustrate that in fission yeast, sp‐Erf2p is the most critical component in selectively palmitoylating Ras at the Golgi for efficient PM localization, and that in mammals, zDHHC9 is now firmly established as a Ras DHHC‐PAT.