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

Padmaja Gade, Amy S. Kimball, Angela C. DiNardo, Priyamvada Gangwal, Douglas D. Ross, H. Scott Boswell, Susan K. Keay, Dhananjaya V. Kalvakolanu

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Expression of DAPK1, a critical regulator of autophagy and apoptosis, is lost in a wide variety of tumors, although the mechanisms are unclear. Atranscription 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.

Original languageEnglish (US)
Pages (from-to)22030-22042
Number of pages13
JournalJournal of Biological Chemistry
Volume291
Issue number42
DOIs
StatePublished - Oct 14 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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