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J. Biol. Chem. 286 (32): 28019-28025

© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Acyl-CoA:Lysophosphatidylcholine Acyltransferase I (Lpcat1) Catalyzes Histone Protein O-Palmitoylation to Regulate mRNA Synthesis*

Chunbin Zou{ddagger}1, Bryon M. Ellis{ddagger}, Rebecca M. Smith{ddagger}, Bill B. Chen{ddagger}, Yutong Zhao{ddagger}, , and Rama K. Mallampalli{ddagger}§

From the {ddagger}Department of Medicine, the Acute Lung Injury Center of Excellence, and
the Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213 and
the §Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania 15240

ABSTRACT Back to Top

Abstract: The enzyme acyl-CoA:lysophosphatidylcholine acyltransferase (Lpcat1) is a critical cytosolic enzyme needed for lung surfactant synthesis that catalyzes an acyltransferase reaction by adding a palmitate to the sn-2 position of lysophospholipids. Here we report that histone H4 protein is subject to palmitoylation catalyzed by Lpcat1 in a calcium-regulated manner. Cytosolic Lpcat1 was observed to shift into the nucleus in lung epithelia in response to exogenous Ca2+. Nuclear Lpcat1 colocalizes with and binds to histone H4, where it catalyzes histone H4 palmitoylation. Mutagenesis studies demonstrated that Ser47 within histone H4 serves as a putative acceptor site, indicative of Lpcat1-mediated O-palmitoylation. Lpcat1 knockdown or expression of a histone H4 Ser47A mutant protein in cells decreased cellular mRNA synthesis. These findings provide the first evidence of a protein substrate for Lpcat1 and reveal that histone lipidation may occur through its O-palmitoylation as a novel post-translational modification. This epigenetic modification regulates global gene transcriptional activity.


Key Words: Calcium • Lung • Nuclear Translocation • Phosphatidylcholine • Phospholipid

Received for publication April 20, 2011. Revision received June 9, 2011.

1 To whom correspondence should be addressed: Dept. of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, BST E1103, 200 Lathrop St., Pittsburgh, PA 15213. Tel.: 412-624-4044; Fax: 412-692-2260; E-mail: zouc{at}upmc.edu.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
SCFFbxw15 Mediates Histone Acetyltransferase Binding to Origin Recognition Complex (HBO1) Ubiquitin-Proteasomal Degradation to Regulate Cell Proliferation.
C. Zou, Y. Chen, R. M. Smith, C. Snavely, J. Li, T. A. Coon, B. B. Chen, Y. Zhao, and R. K. Mallampalli (2013)
J. Biol. Chem. 288, 6306-6316
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