Irradiation with heavy-ion particles changes the cellular distribution of human histone acetyltransferase HAT1.
Hat1 was the first histone acetyltransferase identified; however, its biological function is still unclear. In this report, it is shown for the first time that human Hat1 has two isoforms. Isoform a has 418 amino acids (aa) and is localized exclusively in the nuclear matrix of normal human keratinocytes (NHKs). Isoform b has 334 aa and is located in the cytoplasm, the nucleoplasm, attached to the chromatin and to the nuclear matrix. Immunohistochemical analyses revealed that the bulk of Hat1 is confined to the nucleus, with much lesser amounts in the cytoplasm. Cells undergoing mitotic division have an elevated amount of Hat1 compared to those that are non-mitotic. Senescent cells, however, exhibit a higher concentration of Hat1 in the cytoplasm compare to proliferating cells and the amount of Hat1 in the nucleus decreases with the progression of senescence. NHKs exposed to hydrogen peroxide (H(2)O(2)) or to a beam of high mass and energy ion particles displayed bright nuclear staining for Hat1, a phenotype that was not observed in NHKs exposed to gamma-rays. We established that the enhanced nuclear staining for Hat1 in response to these treatments is regulated by the PI3K and the mitogen-activated protein kinase signaling pathways. Our observations clearly implicate Hat1 in the cellular response assuring the survival of the treated cells.
Biology Department, Brookhaven National Laboratory, 50 Bell Avenue, Building 463, Upton, NY 11973-5000, USA.
Emily A
EA
Lebel
Petra
P
Boukamp
Stefan T
ST
Tafrov
D000107:Acetylation; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002588:Cesium Radioisotopes; D003593:Cytoplasm / Q000378:metabolism; D005720:Gamma Rays; D020450:Heavy Ions; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction
D002588:Cesium Radioisotopes; D006657:Histones; D016877:Oxidants; D006861:Hydrogen Peroxide; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases