Outside the p53 RING: Transcription Regulation by Chromatin-Bound MDM2

Abstract

Evidence mounts, via two studies published in Molecular Cell (Riscal et al., 2016; Wienken et al., 2016), that chromatin-bound MDM2 impacts pluripotency and metabolism to promote survival and proliferation of cancer cells, independently of p53 degradation.

MDM2 and MDMX promote ferroptosis by PPARα-mediated lipid remodeling

“…MDM2 in particular has been shown to have pro-oncogenic activities beyond regulating p53 (Bohlman and Manfredi 2014), and MDM2 can bind to a myriad of proteins, either altering their activity or causing their proteasome-mediated degradation (Fåhraeus and Olivares-Illana 2014). MDM2 has also been shown to regulate gene expression (Biderman et al 2012;Jain and Barton 2016), heterochromatin rearrangement (Mungamuri et al 2016;Wienken et al 2017), DNA repair, and replication (Melo and Eischen 2012;Eischen 2017). Furthermore, this protein has roles in cellular metabolism (Riscal et al 2016), EMT and metastasis (Wang et al 2009;Chen et al 2013;Lu et al 2016;Chen et al 2017a), cell survival and growth (Feeley et al 2017), as well as mitochondrial dynamics (Arena et al 2018).…”