PML/RARA inhibits expression of HSP90 and its target AKT

• DOI: 10.1111/bjh.15715
• Publication Date: 2018-12-10T02:05:32Z
• Authors: Maria Liliana Pir...; Girish Gaur; Gianfranco Catalano; Mariadomenica Divona; Cristina Banella; Serena Travaglini; Maria Carmen Puzz...; Maria Teresa Voso; Francesco Lo‐Coco; Nelida Ines Noguera
• Keywords: Oncogene Proteins, Fusion; Lactams, Macrocyclic; Tretinoin; HSP90AA1 and HSP90AB1; Promyelocytic Leukemia Protein; Transfection; Histones; 03 medical and health sciences; Leukemia, Promyelocytic, Acute; 616; Benzoquinones; Tumor Cells, Cultured; Humans; HSP90 Heat-Shock Proteins; RNA, Messenger; heat shock protein 90; Promoter Regions, Genetic; 0303 health sciences; AKT; Retinoic Acid Receptor alpha; Acute promyelocytic leukaemia; Up-Regulation; Settore MED/15 - MALATTIE DEL SANGUE; HEK293 Cells; PML/RARA; Proto-Oncogene Proteins c-akt; AKT; Acute promyelocytic leukaemia; HSP90AA1 and HSP90AB1; PML/RARA; heat shock protein 90

Summary Essential for cell survival, the 90 kD Heat Shock Proteins ( HSP 90) are molecular chaperons required conformational stabilization and trafficking of numerous client proteins. Functional is stability AKT , a serine‐threonine kinase phosphorylated in response to growth factor stimulation. plays crucial regulatory role differentiation, cycle, transcription, translation, metabolism apoptosis. Acute promyelocytic leukaemia APL ) characterized by presence leukaemia/retinoic acid receptor alpha PML / RARA fusion protein, which deregulates expression several genes involved differentiation Here, we report inhibition AA 1 AB isomer transcription blasts isolated from patients with associated reduction protein loss control on phosphorylation. We show that vitro treatment expressing cells all‐ trans retinoic ATRA up‐regulates stabilizes . Addition 90‐inhibitor 17‐(allylamino)‐17‐demethoxygeldanamycin combination blocks upregulation indicating necessary action This first proving isomers directly differentially repressed critical results cellular homeostasis target proteins, such as blasts.