Journal article
The Transcription Factor ASCIZ and Its Target DYNLL1 Are Essential for the Development and Expansion of MYC-Driven B Cell Lymphoma
DM Wong, L Li, S Jurado, A King, R Bamford, M Wall, MK Walia, GL Kelly, CR Walkley, DM Tarlinton, A Strasser, J Heierhorst
Cell Reports | Published : 2016
Open access
Abstract
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 Eμ-Myc model of lymphoma. Deletion of Asciz or Dynll1 prevented the abnormal expansion of pre-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 DYNLL..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Kimberly Gleeson and Nora Tenis for mouse genotyping and colony management; Michael Thomson for help with FACS analysis and sorting; the St. Vincent's Hospital Bioresources Centre for animal care; Jack Martin and Anne Johnston for comments on the manuscript; David Huang for the BAX antibody; and Michael Reth (Mb1-Cre), Meinrad Busslinger (Cd23-Cre), Jerry Adams (E mu-Myc), Laura Pasqualucci, and Riccardo Dalla-Favera (I mu-Bcl6) for mouse strains. This work was funded by grants from the National Health and Medical Research Council to J.H. (1009763 and 1026125), A.S. (1016701), G.L.K. (1086291), D.M.T. (1054925), and C.R.W. (1065002); the 5point Foundation to J.H., LLS SCOR to A.S. (7001-03), and the Leukemia Foundation to M.W. J.H., D.M.T., and A.S. were supported by NHMRC Research Fellowships; C.R.W. was supported by a Leukemia Foundation Philip Desbrow Research Fellowship; S.J. was supported by a Cancer Council of Victoria Sydney Parker Smith Postdoctoral Research Fellowship; L.L. was supported by a Leukemia Foundation PhD Scholarship; and A.K. was supported by an Australian Postgraduate Award. This work was supported by the Victorian Government's Operational Infrastructure Support Program and the Australian Government NHMRC IRIIS.