title: The Transcription Factor ASCIZ and Its Target DYNLL1 Are Essential for the Development and Expansion of MYC-Driven B Cell Lymphoma.
abstract: How MYC promotes the development of cancer remains to be fully understood. Here, we report that the Zn(2+)-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.
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Wong
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia.
authors.forename: Lingli
authors.initials: L
authors.lastname: Li
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
authors.forename: Sabine
authors.initials: S
authors.lastname: Jurado
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia.
authors.forename: Ashleigh
authors.initials: A
authors.lastname: King
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bamford
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia; Victorian Cancer Cytogenetics Service, St. Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Wall
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
authors.forename: Mannu K
authors.initials: MK
authors.lastname: Walia
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Gemma L
authors.initials: GL
authors.lastname: Kelly
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia.
authors.forename: Carl R
authors.initials: CR
authors.lastname: Walkley
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, VIC 3065, Australia. Electronic address: jheierhorst@svi.edu.au.
authors.forename: Jörg
authors.initials: J
authors.lastname: Heierhorst
mesh_terms: D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D056445:Cytoplasmic Dyneins; D004195:Disease Models, Animal; D004398:Dyneins / Q000172:deficiency / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D016019:Survival Analysis; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*
chemical_list: C554480:ATMIN protein, mouse; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D056445:Cytoplasmic Dyneins; C576160:DYNLL1 protein, mouse; D004398:Dyneins