RETRACTED: Identification of phosphorylated p38 as a novel DAPK-interacting partner during TNFalpha-induced apoptosis in colorectal tumor cells

Am J Pathol. 2009 Aug;175(2):557-70. doi: 10.2353/ajpath.2009.080853. Epub 2009 Jul 23.


Death-associated protein kinase (DAPK) is a serine/threonine kinase that contributes to pro-apoptotic signaling on cytokine exposure. The role of DAPK in macrophage-associated tumor cell death is currently unknown. Recently, we suggested a new function for DAPK in the induction of apoptosis during the interaction between colorectal tumor cells and tumor-associated macrophages. Using a cell-culture model with conditioned supernatants of differentiated/activated macrophages (U937) and human HCT116 colorectal tumor cells, we replicated DAPK-associated tumor cell death; this model likely reflects the in vivo tumor setting. In this study, we show that tumor necrosis factor-alpha exposure under conditions of macrophage activation induced DAPK-dependent apoptosis in the colorectal tumor cell line HCT116. Simultaneously, early phosphorylation of p38 mitogen-activated protein kinase (phospho-p38) was observed. We identified the phospho-p38 mitogen-activated protein kinase as a novel interacting protein of DAPK in tumor necrosis factor-alpha-induced apoptosis. The general relevance of this interaction was verified in two colorectal cell lines without functional p53 (ie, HCT116 p53(-/-) and HT29 mutant) and in human colon cancer and ulcerative colitis tissues. Supernatants of freshly isolated human macrophages were also able to induce DAPK and phospho-p38. Our findings highlight the mechanisms that underlie DAPK regulation in tumor cell death evoked by immune cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line, Tumor
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Death-Associated Protein Kinases
  • Humans
  • Immunoprecipitation
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Macrophage Activation
  • Macrophages / enzymology
  • Phosphorylation
  • Tumor Necrosis Factor-alpha / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Apoptosis Regulatory Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • p38 Mitogen-Activated Protein Kinases