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. Boswell, Susan K. Keay, Dhananjaya V. Kalvakolanu

Research output: Contribution to journalArticle

7 Citations (Scopus)

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
Externally publishedYes

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Activating Transcription Factor 6
Death-Associated Protein Kinases
CCAAT-Enhancer-Binding Proteins
Phosphorylation
Autophagy
B-Cell Chronic Lymphocytic Leukemia
Tumors
Apoptosis
Defects
Processing
Endoplasmic Reticulum
Growth
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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

In: Journal of Biological Chemistry, Vol. 291, No. 42, 14.10.2016, p. 22030-22042.

Research output: Contribution to journalArticle

Gade, Padmaja ; Kimball, Amy S. ; DiNardo, Angela C. ; Gangwal, Priyamvada ; Ross, Douglas D. ; Boswell, H. ; Keay, Susan K. ; Kalvakolanu, Dhananjaya V. / 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. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 42. pp. 22030-22042.
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