Catalytic domain of deubiquitinylase USP48 directs interaction with Rel homology domain of nuclear factor kappaB transcription factor RelA

  • Ahmed Ghanem
  • Katrin Schweitzer
  • Michael NaumannEmail author
Short Communication


The activity and close regulation of nuclear factor kappaB (NF-κB) transcription factors is critical for a variety of cellular processes including inflammation, immunity, differentiation and cell survival. Thus, dysregulation of the NF-κB system could lead to serious diseases, e.g. uncoordinated growth of the normal tissue during the development of cancer. Transcriptional activity of the NF-κB factor RelA is regulated by a number of mechanisms which comprise ubiquitinylation by a multimeric ubiquitin ligase containing Elongins B and C, cullin-2 (Cul2) and suppressor of cytokine signaling 1 (SOCS1), but also USP48-dependent deubiquitinylation. Further, USP48 promotes cell survival and antagonizes also other E3 ligase functions which are involved in genome stability and DNA repair. The regulation of RelA by USP48 has been investigated in detail, but the domains of USP48 and RelA for direct interaction are not known. In this study we report that USP48 interacts physically with RelA in the nucleus. Further, we show by overexpression of truncated proteins that the catalytic USP domain of USP48 interacts with the N-terminal region of the Rel homology domain (RHD) of RelA. This study provides first evidence that the USP domain of USP48 is important for the physical association with substrate proteins, and a suitable target for small molecule inhibitors for therapeutic intervention strategies.


Deubiquitinylase NF-κB Protein domains RelA Transcription factor USP48 



The work was supported by the Ministery of Economy, Science and Digitalisation (Förderung von Wissenschaft und Forschung in Sachsen-Anhalt aus Mitteln der Europäischen Struktur- und Investitionsfonds in der Förderperiode 2014–2020, ZS/2016/04/78155) and a stipend from the Medical Faculty of the Otto von Guericke University to A.G.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interests.

Supplementary material

11033_2019_4587_MOESM1_ESM.pdf (301 kb)
Supplementary material 1 (PDF 300 KB)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Institute of Experimental Internal MedicineOtto von Guericke UniversityMagdeburgGermany

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