title: Death-associated Protein Kinase-1 Expression and Autophagy in Chronic Lymphocytic Leukemia Are Dependent on Activating Transcription Factor-6 and CCAAT/Enhancer-binding Protein-β.
abstract: Expression of DAPK1, a critical regulator of autophagy and apoptosis, is lost in a wide variety of tumors, although the mechanisms are unclear. A transcription factor complex consisting of ATF6 (an endoplasmic reticulum-resident factor) and C/EBP-β is required for the IFN-γ-induced expression of DAPK1 IFN-γ-induced proteolytic processing of ATF6 and phosphorylation of C/EBP-β are obligatory for the formation of this transcriptional complex. We report that defects in this pathway fail to control growth of chronic lymphocytic leukemia (CLL). Consistent with these observations, IFN-γ and chemotherapeutics failed to activate autophagy in CLL patient samples lacking ATF6 and/or C/EBP-β. Together, these results identify a molecular basis for the loss of DAPK1 expression in CLL.
authors: From the Departments of Microbiology and Immunology and.
authors: Padmaja
authors: P
authors: Gade
authors: Medicine and.
authors: Amy S
authors: AS
authors: Kimball
authors: From the Departments of Microbiology and Immunology and.
authors: Angela C
authors: AC
authors: DiNardo
authors: From the Departments of Microbiology and Immunology and.
authors: Priyamvada
authors: P
authors: Gangwal
authors: Medicine and the Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201, and.
authors: Douglas D
authors: DD
authors: Ross
authors: the Indianapolis Veterans Affairs Medical Center, Indianapolis, Indiana 46202.
authors: H Scott
authors: HS
authors: Boswell
authors: Medicine and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201, and.
authors: Susan K
authors: SK
authors: Keay
authors: From the Departments of Microbiology and Immunology and dkalvako@umaryland.edu.
authors: Dhananjaya V
authors: DV
authors: Kalvakolanu
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D064550:Death-Associated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C573415:IFNG protein, human; D009363:Neoplasm Proteins; D007371:Interferon-gamma; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases
keywords: cell signaling; cytokine action; endoplasmic reticulum stress (ER stress); transcription factor; tumor suppressor gene