Interactome Profiling of a Lysine Deacetylase Trapping Probe Library Uncovers Crosstalk Between HDAC6 and NF‐κB Signaling
Abstract
AbstractLysine or histone deacetylases (HDACs) remove acetyl groups from lysine residues of numerous proteins, thereby regulating their function and activity. HDAC6 is involved in multiple cellular processes, yet its protein interaction network remains poorly understood. To uncover novel HDAC6 substrates, we performed an acetylome analysis of HDAC6 knockdown cells, which served as a basis for the design of an HDAC6‐trapping peptide library containing hydroxamic acids. Most probes enriched HDAC6 from cell lysates stronger than HDAC1. Proteomic profiling of the trapping probes revealed a preferential enrichment of HDAC6 and resulted in the identification of novel putative HDAC6 interaction partners. Among those were several components of the pro‐inflammatory transcription factor NF‐κB that were independently confirmed as HDAC6 binders. Mechanistically, HDAC6 counteracted NF‐κB activity induced upon p300‐catalyzed acetylation of NF‐κB p50. These findings indicate a potential anti‐inflammatory function of HDAC6 in NF‐κB signaling.
Article Details
Authors (10)
Julian Seidel
Interfaculty Institute of Biochemistry, University of Tübingen
Caroline Schönfeld
Interfaculty Institute of Biochemistry (IFIB) University of Tübingen Auf der Morgenstelle 34 72076 Tübingen Germany
Julia Sindlinger
Interfaculty Institute of Biochemistry (IFIB) University of Tübingen Auf der Morgenstelle 34 72076 Tübingen Germany
Jürgen Eirich
Plant Physiology, Institute of Plant Biology and Biotechnology, University of Münster
Sören Kirchgäßner
Interfaculty Institute of Biochemistry (IFIB) University of Tübingen Auf der Morgenstelle 34 72076 Tübingen Germany
Nina Kreienkamp
Department of Medicine A, Hematology, Oncology, and Pneumology University Hospital Münster Albert‐Schweitzer‐Campus 1 48149 Münster Germany
Klaus Schulze‐Osthoff
Interfaculty Institute of Biochemistry (IFIB) University of Tübingen Auf der Morgenstelle 34 72076 Tübingen Germany
Iris Finkemeier
Plant Physiology, Institute of Plant Biology and Biotechnology, University of Münster
Stephan Hailfinger
Department of Medicine A, Hematology, Oncology, and Pneumology University Hospital Münster Albert‐Schweitzer‐Campus 1 48149 Münster Germany
Dirk Schwarzer
Interfaculty Institute of Biochemistry, University of Tübingen