This Article Full Text (PDF) Other Versions of this Article: MCB.00662-07v1 28/1/140    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Iizuka, M. Articles by Smith, M. M. Search for Related Content PubMed PubMed Citation Articles by Iizuka, M. Articles by Smith, M. M.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.00662-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Hbo1 Links p53-Dependent Stress Signaling to DNA Replication Licensing

Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908; Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA 22908; Oncogene Division, National Cancer Center Research Institute, Tsukiji, Tokyo 104-0045, Japan; Department of Neuroscience, University of Virginia Health System, Charlottesville, VA 22908

^* To whom correspondence should be addressed. Email: mms7r{at}virginia.edu.

	Abstract

Hbo1 is a histone acetyltransferase (HAT) required for global histone H4 acetylation, steroid-dependent transcription, and chromatin loading of MCM2-7 during DNA replication licensing. It is the catalytic subunit of protein complexes that include ING and JADE proteins, growth regulatory factors and candidate tumor suppressors. These complexes are thought to act via tumor suppressor p53, but the molecular mechanisms, and links between stress signaling and chromatin, are currently unknown. Here we show that p53 physically interacts with Hbo1 and negatively regulates its HAT activity in vitro and in cells. Two physiological stresses that stabilize p53, hyper-osmotic shock and DNA replication fork arrest, also inhibit Hbo1 HAT activity in a p53-dependent manner. Hyperosmotic stress during G1 phase specifically inhibits the loading of the MCM2-7 complex, providing an example of the chromatin output of this pathway. These results reveal a direct regulatory connection between p53-responsive stress signaling and Hbo1-dependent chromatin pathways.