The transcription factor ASCIZ and its target DYNLL1 are essential for the development and expansion of MYC-driven B Cell lymphoma
- Author(s)
- Wong, DM; Li, L; Jurado, S; KING, A; Bamford, R; Wall, M; Walia, MK; Kelly, GL; Walkley, CR; Tarlinton, DM; Strasser, A; Heierhorst, J;
- Details
- Publication Year 2016-02,Volume 14,Issue #6,Page 1488-99
- Journal Title
- Cell Rep
- Publication Type
- Journal Article
- 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 Emu-Myc model of lymphoma. Deletion of Asciz or Dynll1 prevented the abnormal expansion of pre-B cells in pre-cancerous Emu-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 Emu-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.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Genetics Of Cancer; Immunology
- PubMed ID
- 26832406
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2016.01.012
- Open Access at Publisher's Site
http://www.sciencedirect.com.au/science/article/pii/S2211124716000322- NHMRC Grants
- NHMRC/1054925, NHMRC/1016701, NHMRC/1086291,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-03-14 03:05:32
Last Modified: 2016-05-09 12:23:36