The Transcription Factor ASCIZ and Its Target DYNLL1 Are Essential for the Development and Expansion of MYC-Driven B Cell Lymphoma

• Main 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
• Format: Article
• Language: English
• Published: Elsevier 2016-02-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124716000322

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.