title: Neutrophil Elastase in the capacity of the "H2A-specific protease".
abstract: The amino-terminal tail of histones and the carboxy-tail of histone H2A protrude from the nucleosome and can become modified by many different posttranslational modifications (PTM). During a mass spectrometric proteome analysis on haematopoietic cells we encountered a histone PTM that has received only little attention since its discovery over 35 years ago: truncation of the histone H2A C-tail at V114 which is mediated by the "H2A specific protease" (H2Asp). This enzyme is still referenced today but it was never identified. We first developed a sensitive AQUA approach for specific quantitation of the H2AV114 clipping. This clipping was found only in myeloid cells and further cellular fractionation lead to the annotation of the H2Asp as Neutrophil Elastase (NE). Ultimate proof was provided by NE incubation experiments and by studying histone extracts from NE Null mice. The annotation of the H2Asp not only is an indispensable first step in elucidating the potential biological role of this enzymatic interaction but equally provides the necessary background to critically revise earlier reports of H2A clipping.
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Dhaenens
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Glibert
authors.affiliation: Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Lambrecht
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Vossaert
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Van Steendam
authors.affiliation: Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Elewaut
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Electronic address: dieter.deforce@ugent.be.
authors.forename: D
authors.initials: D
authors.lastname: Deforce
mesh_terms: D000818:Animals; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D051379:Mice; D013379:Substrate Specificity
chemical_list: D010450:Endopeptidases; D019272:Leukocyte Elastase; C021361:histone proteases
keywords: AQUA; H2A specific protease; H2AV(114); Histone clipping; Neutrophil Elastase