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Review
. 2021 Aug 28;9(1):66.
doi: 10.1186/s40364-021-00320-w.

Deubiquitinases in hematological malignancies

Hu Lei  1 , Jiaqi Wang  2 , Jiacheng Hu  2 , Qian Zhu  2 , Yingli Wu  3
Affiliations
Review

Deubiquitinases in hematological malignancies

Hu Lei et al. Biomark Res. .

Abstract

Deubiquitinases (DUBs) are enzymes that control the stability, interactions or localization of most cellular proteins by removing their ubiquitin modification. In recent years, some DUBs, such as USP7, USP9X and USP10, have been identified as promising therapeutic targets in hematological malignancies. Importantly, some potent inhibitors targeting the oncogenic DUBs have been developed, showing promising inhibitory efficacy in preclinical models, and some have even undergone clinical trials. Different DUBs perform distinct function in diverse hematological malignancies, such as oncogenic, tumor suppressor or context-dependent effects. Therefore, exploring the biological roles of DUBs and their downstream effectors will provide new insights and therapeutic targets for the occurrence and development of hematological malignancies. We summarize the DUBs involved in different categories of hematological malignancies including leukemia, multiple myeloma and lymphoma. We also present the recent development of DUB inhibitors and their applications in hematological malignancies. Together, we demonstrate DUBs as potential therapeutic drug targets in hematological malignancies.

Keywords: Deubiquitinases; Hematological malignancies; Leukemia; Lymphoma; Multiple myeloma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Human DUBs. Human DUBs are composed of cysteine proteases and metalo proteases. According to their domain structure, DUBs are classified in to six families: the ubiquitin-specific proteases (USPs), the ubiquitin carboxy-terminal hydrolases (UCHs), the ovarian tumor-related proteases (OTUs), the Machado-Joseph disease protein domain proteases (MJDs), the JAB1/PAB1/MPN-domain containing metallo-enzyme (JAMMs), and the motif interacting with Ub-containing novel DUB family (MINDYs)
Fig. 2
Fig. 2
DUBs in chronic myeloid leukemia. The red arrows represent oncogenes and the green arrows represent tumor suppressors in CML. The surrounding text describes the substrates or signaling pathways or effects of DUBs
Fig. 3
Fig. 3
DUBs in acute myeloid leukemia. The red arrows represent oncogenes and the green arrows represent tumor suppressors in AML. USP22 acts as an oncogene or tumor suppressor in AML, depending on the context. The surrounding text describes the substrates or related proteins of DUBs in AML
Fig. 4
Fig. 4
DUBs in acute lymphoblastic leukemia. The red arrows represent oncogenes and the green arrows represent tumor suppressors in ALL. The surrounding text describes the substrates or signaling pathways involved in DUBs of different types of ALL
Fig. 5
Fig. 5
DUBs in multiple myeloma. The red arrows represent oncogenes and the green arrows represent tumor suppressors in MM. The surrounding text describes the substrates or signaling pathways of DUBs in MM
Fig. 6
Fig. 6
DUBs in non-hodgkin lymphoma. The red arrows represent oncogenes and the green arrows represent tumor suppressors in NHL. The surrounding text describes the substrates or signaling pathways involved in DUBs of different types of lymphoma. CRLs: cullin-RING E3 ubiquitin ligases
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