Deregulated expression of the HSP40 family members Auxilin-1 and -2 is indicative of proteostasis imbalance and predicts patient outcome in Ph+ leukemia

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• 作者：Margherita Vieri ; Huimin Geng ; John B. Patterson…
• 关键词：Unfolded protein response ; Acute lymphoblastic leukemia ; Chronic myeloid leukemia ; HSP40 ; DNAJ ; Auxilin ; 1 ; Auxilin ; 2
• 刊名：Experimental Hematology & Oncology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：5
• 期：1
• 全文大小：1,502 KB
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• 作者单位：Margherita Vieri (1)
  Huimin Geng (2)
  John B. Patterson (3)
  Jens Panse (1)
  Stefan Wilop (1)
  Afshin Samali (4) (5)
  Eric Chevet (6) (7)
  Behzad Kharabi Masouleh (1)
  
  1. Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany
  2. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, 94143, USA
  3. MannKind Corporation, Valencia, CA, USA
  4. Apoptosis Research Centre, National University of Ireland, Galway, Ireland
  5. Department of Biochemistry, National University of Ireland, Galway, Ireland
  6. INSERM ERL440, Oncogenesis, Stress and Signaling, Université Rennes 1, Rennes, France
  7. Centre de Lutte Contre Le Cancer Eugène Marquis, Rennes, France
  
• 刊物主题：Hematology; Oncology;
• 出版者：BioMed Central
• ISSN：2162-3619

文摘

Background Proteostasis is defined by the orchestrated control of anabolic and catabolic protein pathways. Disruption of proteostasis results in cell stress and adaptation to proteostasis imbalance is mediated by adaptive pathways such as the Heat Shock Response (including heat-shock proteins) or the unfolded protein response (UPR). The BCR-ABL1 kinase (Philadelphia chromosome) is the hallmark of chronic myeloid leukemia (CML) and defines a historically poor subset in acute lymphoblastic leukemia (Ph+ ALL). We previously demonstrated the importance of the UPR and particularly of the IRE1/XBP1 signaling axis in Ph+ ALL, while others demonstrated the therapeutic relevance of HSP70 in ALL. In this regard, HSP70 is regulated by smaller HSP40 s, whose function is so far poorly characterized.