Regulation of the localisation and function of the oncogene LYRIC/AEG-1 by ubiquitination at K486 and K491.

ABSTRACT: The pivotal role of LYRIC/AEG-1 in malignant transformation, tumourigenesis and chemo-resistance has previously been demonstrated in different cell types and sub-cellular compartments. The localisation of LYRIC/AEG-1 appears crucial to its function and is regulated by three lysine-rich nuclear localisation signal regions, one of which was previously demonstrated to be modified by ubiquitin. Here we show that mutation of LYRIC/AEG-1 at K486 and K491 results in a loss of ubiquitination. A K486/491R double mutant that is incapable of ubiquitination shows reduced binding to the NFκB subunit p65 or importin-β resulting in a distinctive peri-nuclear localisation of LYRIC/AEG-1. We also provide evidence to suggest that TOPORS, an E3 ligase that also regulates p53 modification may be responsible f

SUBMITTER: Luxton HJ 

PROVIDER: S-EPMC4013555 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature