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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
Wong, David M. Li, ngli Li Jurado, Sabine King, Ashleigh Bamford, Rebecca Wall, Meaghan Walia, Mannu K. Kelly, Gemma L. Walkley, Carl R. Tarlinton, David M.
Wong, David M.
Li, ngli Li
Jurado, Sabine
King, Ashleigh
Bamford, Rebecca
Wall, Meaghan
Walia, Mannu K.
Kelly, Gemma L.
Walkley, Carl R.
Tarlinton, David M.
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-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.
Keywords
Date
2016
Type
Journal article
Journal
Cell Reports
Book
Volume
14
Issue
6
Page Range
1488-1499
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
File Access
Open