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The Transcription Factor ASCIZ and Its Target DYNLL1 Are Essential for the Development and Expansion of MYC-Driven B Cell Lymphoma.

Abstract
How MYC promotes the development of cancer remains to be fully understood. Here, we report that the Zn(2+)-finger transcription factor ASCIZ (ATMIN, ZNF822) synergizes with MYC to activate the expression of dynein light chain (DYNLL1, LC8) in the murine Eμ-Myc model of lymphoma. Deletion of Asciz or Dynll1 prevented the abnormal expansion of pre-B cells in pre-cancerous Eμ-Myc mice and potentiated the pro-apoptotic activity of MYC in pre-leukemic immature B cells. Constitutive loss of Asciz or Dynll1 delayed lymphoma development in Eμ-Myc mice, and induced deletion of Asciz in established lymphomas extended the survival of tumor-bearing mice. We propose that ASCIZ-dependent upregulation of DYNLL1 levels is essential for the development and expansion of MYC-driven lymphomas by enabling the survival of pre-neoplastic and malignant cells.
AuthorsDavid M Wong, Lingli Li, Sabine Jurado, Ashleigh King, Rebecca Bamford, Meaghan Wall, Mannu K Walia, Gemma L Kelly, Carl R Walkley, David M Tarlinton, Andreas Strasser, Jörg Heierhorst
JournalCell reports (Cell Rep) Vol. 14 Issue 6 Pg. 1488-1499 (Feb 16 2016) ISSN: 2211-1247 [Electronic] United States
PMID26832406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • ATMIN protein, mouse
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Cytoplasmic Dyneins
  • DYNLL1 protein, mouse
  • Dyneins
Topics
  • Animals
  • Apoptosis
  • B-Lymphocytes (immunology, pathology)
  • Cell Cycle (genetics)
  • Cell Differentiation
  • Cell Proliferation
  • Cytoplasmic Dyneins
  • Disease Models, Animal
  • Dyneins (deficiency, genetics)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, B-Cell (genetics, immunology, mortality, pathology)
  • Mice
  • Precursor Cells, B-Lymphoid (immunology, pathology)
  • Proto-Oncogene Proteins c-myc (genetics, immunology)
  • Signal Transduction
  • Survival Analysis
  • Transcription Factors (deficiency, genetics)

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