Rosebeck S, Lim MS, Elenitoba-Johnson KSJ, McAllister-Lucas LM, Lucas PC. API2-MALT1 oncoprotein promotes lymphomagenesis via unique program of substrate ubiquitination and proteolysis. World J Biol Chem 2016; 7(1): 128-137 [PMID: 26981201 DOI: 10.4331/wjbc.v7.i1.128]
Corresponding Author of This Article
Peter C Lucas, MD, PhD, Department of Pathology and Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States. lucaspc@upmc.edu
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Biol Chem. Feb 26, 2016; 7(1): 128-137 Published online Feb 26, 2016. doi: 10.4331/wjbc.v7.i1.128
API2-MALT1 oncoprotein promotes lymphomagenesis via unique program of substrate ubiquitination and proteolysis
Shaun Rosebeck, Megan S Lim, Kojo S J Elenitoba-Johnson, Linda M McAllister-Lucas, Peter C Lucas
Shaun Rosebeck, Department of Medicine, University of Chicago, Chicago, IL 60637, United States
Megan S Lim, Kojo SJ Elenitoba-Johnson, Department of Pathology and Laboratory Medicine, Stellar-Chance Laboratories, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States
Linda M McAllister-Lucas, Department of Pediatrics, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States
Linda M McAllister-Lucas, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, United States
Peter C Lucas, Department of Pathology and Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States
Author contributions: Rosebeck S wrote the draft manuscript; Lim MS, Elenitoba-Johnson KSJ, McAllister-Lucas LM and Lucas PC revised the manuscript and contributed additional sections.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Peter C Lucas, MD, PhD, Department of Pathology and Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, United States. lucaspc@upmc.edu
Telephone: +1-412-6926218 Fax: +1-412-6927816
Received: July 9, 2015 Peer-review started: July 14, 2015 First decision: October 13, 2015 Revised: November 17, 2015 Accepted: December 7, 2015 Article in press: December 8, 2015 Published online: February 26, 2016
Core Tip
Core tip: We summarize the identification of novel API2-mucosa-associated lymphoid tissue (MALT) 1-interacting proteins that uniquely mediate the cellular effects of the fusion oncoprotein but not wild-type API2 or MALT1. API2-MALT1 recruits receptor interacting protein 1 and tumor necrosis factor (TNF) receptor associated factor 2, which normally function downstream of the TNF receptor, and utilizes these proteins to communicate unregulated canonical nuclear factor-κB (NF-κB) in a manner that does not depend on the protease activity of MALT1. Simultaneously, NF-κB inducing kinase is recruited to API2-MALT1 and is proteolytically cleaved by the MALT1 protease domain to generate a stable, non-canonical NF-κB-activating fragment. Finally, LIM domain and actin-binding protein 1 is similarly recruited and cleaved as an API2-MALT1 specific target and its cleavage mediates an NF-κB-independent mechanism of oncogenesis. Additional factors, including SMAC and BCL10, may also play key roles as API2-MALT1 binding partners and downstream signaling factors. Thus, the API2-MALT1 fusion utilizes a distinct set of protein-protein interactions to leverage multiple, divergent mechanisms and achieve potent oncogenic reprogramming of affected B cells.
