Journal
CELL REPORTS
Volume 14, Issue 6, Pages 1488-1499Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.01.012
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Categories
Funding
- National Health and Medical Research Council [1009763, 1026125, 1016701, 1086291, 1054925, 1065002]
- 5point Foundation
- LLS SCOR
- Leukemia Foundation
- NHMRC Research Fellowships
- Leukemia Foundation Philip Desbrow Research Fellowship
- Cancer Council of Victoria Sydney Parker Smith Postdoctoral Research Fellowship
- Leukemia Foundation PhD Scholarship
- Australian Postgraduate Award
- Victorian Government's Operational Infrastructure Support Program
- Australian Government NHMRC IRIIS
- National Health and Medical Research Council of Australia [1065002, 1086291] Funding Source: NHMRC
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How MYC promotes the development of cancer remains to be fully understood. Here, we report that the Zn2+-finger transcription factor ASCIZ (ATMIN, ZNF822) synergizes with MYC to activate the expression of dynein light chain (DYNLL1, LC8) in the murine Em-Myc model of lymphoma. Deletion of Asciz or Dynll1 prevented the abnormal expansion of pre-B cells in pre-cancerous Em-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 Em-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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