Abstract |
Protein lysine acetylation is one of the major posttranslational modifications (PTMs) with several thousands of proteins identified to be acetylated in mammalian tissues. Mechanistic studies have revealed important functions of acetylation in the regulation of protein function. Much less is known on how the acetyltransferases themselves are regulated. In the current study, we discover that the Elongator protein 3 (ELP3) acetyltransferase is modified by tyrosine phosphorylation. We demonstrate that the anaplastic lymphoma kinase (ALK) is the major tyrosine kinase responsible for ELP3 tyrosine phosphorylation. ELP3 is phosphorylated in tumor cells expressing oncogenic NPM-ALK fusion protein. We further identify Tyr202 as the major ALK phosphorylation site in ELP3. Importantly, the introduction of Y202 phosphorylation mutant ELP3 into ALK-positive tumor cells reduced cell growth and impaired gene expression. Collectively, our study reveals a novel regulatory mechanism for ELP3, provides an example that acetyltransferase itself can be regulated by PTM, and suggests a potential target for ALK-positive cancer therapies.
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Authors | Meng-Tian Li, Jun-Yun Liang, Yi-Ping Sun, Jian Jin, Yue Xiong, Kun-Liang Guan, Hai-Xin Yuan |
Journal | The Biochemical journal
(Biochem J)
Vol. 476
Issue 15
Pg. 2239-2254
(08 15 2019)
ISSN: 1470-8728 [Electronic] England |
PMID | 31341009
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society. |
Chemical References |
- Nerve Tissue Proteins
- Oncogene Proteins, Fusion
- ELP3 protein, human
- Histone Acetyltransferases
- p80(NPM-ALK) protein
- Protein-Tyrosine Kinases
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Topics |
- Amino Acid Substitution
- HCT116 Cells
- HEK293 Cells
- Histone Acetyltransferases
(genetics, metabolism)
- Humans
- Mutation, Missense
- Neoplasms
(enzymology, genetics, pathology)
- Nerve Tissue Proteins
(genetics, metabolism)
- Oncogene Proteins, Fusion
(genetics, metabolism)
- Phosphorylation
- Protein-Tyrosine Kinases
(genetics, metabolism)
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