title: Programming cancer cells for high expression levels of Mcl1.
abstract: The Bcl2 pro-survival protein family has long been recognized for its important contributions to cancer. At elevated levels relative to pro-apoptotic effector members, the survival proteins prevent cancer cells from initiating apoptosis in the face of many intrinsic tumour-suppressing pathways and extrinsic therapeutic treatments aimed at controlling tumorigenesis. Recent studies, including genome-wide analyses, have begun to focus attention on a particularly enigmatic member of the family-myeloid cell leukaemia 1 (Mcl1). For reasons that are not clear, Mcl1 in cancer cells is turned over rapidly, eliminated primarily through the ubiquitin-proteasome pathway. Moreover, the mechanistic aspects of this constitutive membrane-associated protein have not been fully elucidated. As the pro-cancer activity of Mcl1 requires elevated expression levels of the protein, the cancer genome adapts to ensure either high levels of synthesis or evasion of degradation, or both. Here, we focus on the complex strategies at play and their therapeutic implications.
authors.affiliation: Department of Biochemistry, and Goodman Cancer Research Center, McGill University, Montréal, Québec H3G 2J7, Canada.
authors.forename: Franziska
authors.initials: F
authors.lastname: Ertel
authors.forename: Mai
authors.initials: M
authors.lastname: Nguyen
authors.forename: Anne
authors.initials: A
authors.lastname: Roulston
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Shore
mesh_terms: D000818:Animals; D017209:Apoptosis; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2