Linking the SUMO protease SENP5 to neutrophil differentiation of AML cells

Elena A Federzoni; Severin Gloor; Jing Jin; Deborah Shan-Krauer; Martin F Fey; Bruce E Torbett; Mario P Tschan

doi:10.1016/j.lrr.2015.04.002

Linking the SUMO protease SENP5 to neutrophil differentiation of AML cells

Leuk Res Rep. 2015 Apr 23;4(1):32-5. doi: 10.1016/j.lrr.2015.04.002. eCollection 2015.

Authors

Elena A Federzoni¹, Severin Gloor², Jing Jin³, Deborah Shan-Krauer², Martin F Fey⁴, Bruce E Torbett⁵, Mario P Tschan³

Affiliations

¹ Division of Experimental Pathology, Institute of Pathology, University of Bern, Switzerland ; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, United States.
² Division of Experimental Pathology, Institute of Pathology, University of Bern, Switzerland.
³ Division of Experimental Pathology, Institute of Pathology, University of Bern, Switzerland ; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
⁴ Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.
⁵ Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, United States.

Abstract

In an mRNA profiling screen performed to unveil novel mechanisms of leukemogenesis, we found that the sentrin-specific protease 5 (SENP5) was significantly repressed in clinical acute myeloid leukemia when compared to healthy neutrophil samples. SENP5 is an enzyme that targets and cleaves small ubiquitin-like modifier (SUMO) residues from SUMOylated proteins. Further investigation with AML neutrophil differentiation cell models showed increased SENP5 expression upon induction of differentiation; in contrast, knocking down SENP5 resulted in significantly attenuated neutrophil differentiation. Our results support a new role of SENP5 in AML pathology, and in particular in the neutrophil differentiation of myeloid leukemic cells.

Keywords: AML; Acute myeloid leukemia; Neutrophil differentiation; SENP5; SUMO protease.