Journal article

Consequences of Zmat3 loss in c-MYC- and mutant KRAS-driven tumorigenesis

Sarah A Best, Cassandra J Vandenberg, Etna Abad, Lachlan Whitehead, Laia Guiu, Sheryl Ding, Margs S Brennan, Andreas Strasser, Marco J Herold, Kate D Sutherland, Ana Janic

Cell Death and Disease | SPRINGERNATURE | Published : 2020

Abstract

TP53 is a critical tumor suppressor that is mutated in approximately 50% of human cancers. Unveiling the downstream target genes of TP53 that fulfill its tumor suppressor function is an area of intense investigation. Zmat3 (also known as Wig-1 or PAG608) is one such downstream target of p53, whose loss in hemopoietic stem cells lacking the apoptosis and cell cycle regulators, Puma and p21, respectively, promotes the development of leukemia. The function of Zmat3 in tumorigenesis however remains unclear. Here, to investigate which oncogenic drivers co-operate with Zmat3 loss to promote neoplastic transformation, we utilized Zmat3 knockout mice in models of c-MYC-driven lymphomagenesis and Kra..

View full abstract

Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by Leukemia and Lymphoma Society of America


Awarded by Cancer Council of Victoria Project


Awarded by Spanish Ministry of Economy and Development Grant


Awarded by Victorian Cancer Agency Mid-Career Research Fellowship


Awarded by Ramon y Cajal Fellowship


Awarded by NHMRC Fellowships


Awarded by "Maria de Maeztu" Programme for Units of Excellence in RD


Awarded by La Caixa banking foundation


Funding Acknowledgements

We are grateful to C. Gatt, K. McKenzie, S. Oliver and G. Siciliano for expert animal care; B. Helbert, K. Mackwell, and R. Chan for genotyping; E. Tsui in the WEHI Histology Facility and S. Monard in the WEHI Flow Cytometry Facility for expert support; E. Michalak for providing animal data and discussions. This work was supported by the Australian Phenomics Network (APN); the Australian National Health and Medical Research Council (NHMRC) Project Grant to M.J.H. (1145728), to M.J.H. and A.S. (1143105), Program Grant to A.S. (1016701); the Leukemia and Lymphoma Society of America to A.S. and M.J.H. (LLS SCOR 7001-13); the Cancer Council of Victoria Project grant to A.S. (1052309) and Venture Grant to M.J.H. and A.S.; support to A.S. from the estate of Anthony (Toni) Redstone OAM and a Spanish Ministry of Economy and Development Grant to A.J. (RTI2018-099017-A-I00). K.D.S. is supported by a Victorian Cancer Agency Mid-Career Research Fellowship (18003) and the Peter and Julie Alston Centenary Fellowship, A.J. is supported by Ramon y Cajal Fellowship (RYC2018-025244-I), A.S. and M.J.H. are supported by NHMRC Fellowships (1020363 and 1156095), M.S.B is supported by Cancer Council Victoria Postdoctoral Fellowship. This work was made possible through the Victorian Government Operational Infrastructure Support and Australian Government, a "Maria de Maeztu" Programme for Units of Excellence in R&D MDM-2014-0370 (Government of Spain) and La Caixa banking foundation (51110009).