Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth
Jonathan B Baell, David J Leaver, Stefan J Hermans, Gemma L Kelly, Margs S Brennan, Natalie L Downer, Nghi Nguyen, Johannes Wichmann, Helen M Mcrae, Yuqing Yang, Ben Cleary, H Rachel Lagiakos, Stephen Mieruszynski, Guido Pacini, Hannah K Vanyai, Maria I Bergamasco, Rose E May, Bethany K Davey, Kimberly J Morgan, Andrew J Sealey Show all
NATURE | NATURE RESEARCH | Published : 2018
Acetylation of histones by lysine acetyltransferases (KATs) is essential for chromatin organization and function1. Among the genes coding for the MYST family of KATs (KAT5-KAT8) are the oncogenes KAT6A (also known as MOZ) and KAT6B (also known as MORF and QKF)2,3. KAT6A has essential roles in normal haematopoietic stem cells4-6 and is the target of recurrent chromosomal translocations, causing acute myeloid leukaemia7,8. Similarly, chromosomal translocations in KAT6B have been identified in diverse cancers8. KAT6A suppresses cellular senescence through the regulation of suppressors of the CDKN2A locus9,10, a function that requires its KAT activity10. Loss of one allele of KAT6A extends the m..View full abstract
Awarded by Australian Government through NHMRC project
We thank F. Dabrowski, C. D'Alessandro, WEHI Bioservices, the WEHI FACS laboratory, the MX2 beamline staff at the Australian Synchrotron for their expert help and Z. Gong for the two transgenic zebrafish lines. This work was funded by the Australian Government through NHMRC project grants 1030704, 1080146, Research Fellowships (T.T., A.K.V., G.K.S., J.K.H., M.W.P. and J.B.), the NHMRC IRIISS and the Cancer Therapeutics Cooperative Research Centre. The Victorian State Government OIS Grants to WEHI, Monash and St Vincent's Institute are gratefully acknowledged.