title: Novel strategies to target the ubiquitin proteasome system in multiple myeloma.
abstract: Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of plasma cells in the bone marrow (BM). The success of the proteasome inhibitor bortezomib in the treatment of MM highlights the importance of the ubiquitin proteasome system (UPS) in this particular cancer. Despite the prolonged survival of MM patients, a significant amount of patients relapse or become resistant to therapy. This underlines the importance of the development and investigation of novel targets to improve MM therapy. The UPS plays an important role in different cellular processes by targeted destruction of proteins. The ubiquitination process consists of enzymes that transfer ubiquitin to proteins targeting them for proteasomal degradation. An emerging and promising approach is to target more disease specific components of the UPS to reduce side effects and overcome resistance. In this review, we will focus on different components of the UPS such as the ubiquitin activating enzyme E1, the ubiquitin conjugating enzyme E2, the E3 ubiquitin ligases, the deubiquitinating enzymes (DUBs) and the proteasome. We will discuss their role in MM and the implications in drug discovery for the treatment of MM.
authors.affiliation: Laboratory of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lub
authors.affiliation: Laboratory of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Ken
authors.initials: K
authors.lastname: Maes
authors.affiliation: Laboratory of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Eline
authors.initials: E
authors.lastname: Menu
authors.affiliation: Laboratory of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: De Bruyne
authors.affiliation: Laboratory of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Vanderkerken
authors.affiliation: Laboratory of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Van Valckenborgh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors*; D054875:Ubiquitination / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: multiple myeloma; ubiquitin proteasome system