MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway

Oncogene
Bilal N SheikhTim Thomas

Abstract

Cellular senescence is an important mechanism that restricts tumour growth. The Ink4a-Arf locus (also known as Cdkn2a), which encodes p16(INK4A) and p19(ARF), has a central role in inducing and maintaining senescence. Given the importance of cellular senescence in restraining tumour growth, great emphasis is being placed on the identification of novel factors that can modulate senescence. The MYST-family histone acetyltransferase MOZ (MYST3, KAT6A), first identified in recurrent translocations in acute myeloid leukaemia, has been implicated in both the promotion and inhibition of senescence. In this study, we investigate the role of MOZ in cellular senescence and show that MOZ is a potent inhibitor of senescence via the INK4A-ARF pathway. Primary mouse embryonic fibroblasts (MEFs) isolated from Moz-deficient embryos exhibit premature senescence, which was rescued on the Ink4a-Arf(-/-) background. Importantly, senescence resulting from the absence of MOZ was not accompanied by DNA damage, suggesting that MOZ acts independently of the DNA damage response. Consistent with the importance of senescence in cancer, expression profiling revealed that genes overexpressed in aggressive and highly proliferative cancers are expressed at lo...Continue Reading

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Citations

Feb 9, 2016·Experimental Hematology·Anne LargeotGeorges Lacaud
Oct 25, 2016·Experimental Hematology·Bilal N SheikhTim Thomas
Apr 4, 2016·Mechanisms of Ageing and Development·Kalpana MujooTej K Pandita
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Nov 6, 2018·Nature Reviews. Genetics·Bilal N Sheikh, Asifa Akhtar
Feb 18, 2020·Future Medicinal Chemistry·Xiangyan YiJonathan B Baell
Oct 24, 2017·Molecular & Cellular Oncology·C GamellY Haupt
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Jan 6, 2021·Journal of Cell Communication and Signaling·Andrés Hernández-OliverasJuan Santiago-García
Mar 24, 2021·Briefings in Functional Genomics·Azucena RochaNicola Neretti
Aug 31, 2021·Frontiers in Cell and Developmental Biology·Jing YangXing Zhang
Oct 26, 2021·Pediatric Hematology and Oncology·Chengfang ZhangYong Sun

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