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Review
. 2015 Jul;22(4):369-78.
doi: 10.1097/MOH.0000000000000156.

The role of aberrant proteolysis in lymphomagenesis

Anagh A Sahasrabuddhe  1 , Kojo S J Elenitoba-Johnson
Affiliations
Review

The role of aberrant proteolysis in lymphomagenesis

Anagh A Sahasrabuddhe et al. Curr Opin Hematol. 2015 Jul.

Abstract

Purpose of review: Deregulated proteolysis is increasingly being implicated in pathogenesis of lymphoma. In this review, we highlight the major cellular processes that are affected by deregulated proteolysis of critical substrates that promote lymphoproliferative disorders.

Recent findings: Emerging evidence supports the role of aberrant proteolysis by the ubiquitin proteasome system (UPS) in lymphoproliferative disorders. Several UPS mediators are identified to be altered in lymphomagenesis. However, the precise role of their alteration and comprehensive knowledge of their target substrate critical for lymphomagenesis is far from complete.

Summary: Many E3 ligase and deubiquitinases that contribute to regulated proteolysis of substrates critical for major cellular processes are altered in various lineages of lymphoma. Understanding of the proteolytic regulatory mechanisms of these major cellular pathways may offer novel biomarkers and targets for lymphoma therapy.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
A multistep enzymatic cascade attaches ubiquitin (Ub) to its Substrate. An E1 (ubiquitin activating enzyme) activate ubiquitin using energy from ATP hydrolysis and transfers it to an E2 (ubiquitin conjugating enzyme. The E2 subsequently transfer the activated ubiquitin to a substrate that is specifically recruited by an E3 (ubiquitin ligase). Polyubiquitination comprising four or more ubiquitin protein linked either through K48 or K11 undergo degradation in 26S proteasome. The ubiquitination mark can be reversed by deubiquitinase enzymes (DUBs) to protect substrate from degradation. The dynamic equilibrium of E3 ligase and DUBs dictates the level of substrate steady state levels and turnover.
FIGURE 2
FIGURE 2
Aberrant proteolysis of critical substrates involved in cell-cycle progression, genotoxic stress, apoptosis, or cellular machinery such as epigenetic modulators and transcription factors that control gene expression contribute to lymphoma development and evolution.
See this image and copyright information in PMC

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