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.
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Authors | David 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 |
Journal | Cell reports
(Cell Rep)
Vol. 14
Issue 6
Pg. 1488-1499
(Feb 16 2016)
ISSN: 2211-1247 [Electronic] United States |
PMID | 26832406
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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