title: PML tumour suppression and beyond: therapeutic implications.
abstract: Recognition of the tumour suppressive capacity of the Promyelocytic Leukemia protein (PML) has emerged beyond its identification through APL, to a broad spectrum of tumors. This ability has chiefly been linked to its role as a core component of dynamic structures termed PML Nuclear Bodies (PML-NBs). In response to a variety of stresses, key factors and their molecular modifiers are recruited to PML-NBs, where activating modifications are facilitated, leading to a cellular stress response. PML was also found to perform anti-tumourigenic functions through cytoplasmic activities. Surprisingly, important recent research defined growth promoting capabilities of PML, which significantly challenges the notion of a 'classic' tumour suppressor. Through metabolic reprogramming, PML can afford a selective advantage for tumor cells in certain settings. The multiple forms in which PML exists are the likely explanation of this functional diversity. This behavioral ambiguity however raises a significant challenge to the design of strategies to therapeutically target PML. In this review we discuss this change of paradigm in the PML field and its ramifications, particularly for tailoring cancer therapies.
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, East Melbourne 3002, Victoria, Australia.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gamell
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, East Melbourne 3002, Victoria, Australia.
authors.forename: Piotr
authors.initials: P
authors.lastname: Jan Paul
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, East Melbourne 3002, Victoria, Australia; Sir Peter MacCallum Department of Oncology, the University of Melbourne, Parkville 3010, Victoria, Australia; Department of Pathology, the University of Melbourne, Parkville 3010, Victoria, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton 3168, Australia. Electronic address: ygal.haupt@petermac.org.
authors.forename: Ygal
authors.initials: Y
authors.lastname: Haupt
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, East Melbourne 3002, Victoria, Australia; Sir Peter MacCallum Department of Oncology, the University of Melbourne, Parkville 3010, Victoria, Australia.
authors.forename: Sue
authors.initials: S
authors.lastname: Haupt
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human
keywords: Isoform; PML nuclear bodies; Promyelocytic leukemia; Promyelocytic leukemia protein; Tumour suppression