Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

The tumor suppressor gene DAPK2 is induced by the myeloid transcription factors PU.1 and C/EBPalpha during granulocytic differentiation but repressed by PML-RARalpha in APL

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Humbert, M.
  • Federzoni, E. A.
  • Britschgi, A.
  • Schlaefli, A. M.
  • Valk, P. J. M.
  • Kaufmann, T.
  • Haferlach, T.
  • Behre, G.
  • Simon, H. U.
  • Torbett, Bruce
  • Fey, M. F.
  • Tschan, M. P.

publication date

  • January 2014

journal

  • Journal of Leukocyte Biology  Journal

abstract

  • DAPK2 is a proapoptotic protein that is mostly expressed in the hematopoietic tissue. A detailed DAPK2 expression analysis in two large AML patient cohorts revealed particularly low DAPK2 mRNA levels in APL. DAPK2 levels were restored in APL patients undergoing ATRA therapy. PML-RARA is the predominant lesion in APL causing transcriptional repression of genes important for neutrophil differentiation. We found binding of PML-RARA and PU.1, a myeloid master regulator, to RARA and PU.1 binding sites in the DAPK2 promoter. Ectopic expression of PML-RARA in non-APL, as well as knocking down PU.1 in APL cells, resulted in a significant reduction of DAPK2 expression. Restoring DAPK2 expression in PU.1 knockdown APL cells partially rescued neutrophil differentiation, thereby identifying DAPK2 as a relevant PU.1 downstream effector. Moreover, low DAPK2 expression is also associated with C/EBPα-mutated AML patients, and we found C/EBPα-dependent regulation of DAPK2 during APL differentiation. In conclusion, we identified first inhibitory mechanisms responsible for the low DAPK2 expression in particular AML subtypes, and the regulation of DAPK2 by two myeloid transcription factors underlines its importance in neutrophil development.

subject areas

  • CCAAT-Enhancer-Binding Protein-alpha
  • Cell Differentiation
  • Cell Line, Tumor
  • Death-Associated Protein Kinases
  • Gene Expression Regulation
  • Granulocytes
  • Humans
  • Leukemia, Myeloid, Acute
  • Leukemia, Promyelocytic, Acute
  • Neutrophils
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Transcription, Genetic
scroll to property group menus

Research

keywords

  • APL
  • DRP-1
  • acute myeloid leukemia
  • neutrophil
scroll to property group menus

Identity

PubMed Central ID

  • PMC3868189

International Standard Serial Number (ISSN)

  • 0741-5400

Digital Object Identifier (DOI)

  • 10.1189/jlb.1112608

PubMed ID

  • 24038216
scroll to property group menus

Additional Document Info

start page

  • 83

end page

  • 93

volume

  • 95

issue

  • 1

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support