Consequences of ubiquitin E2 enzyme (E2-25K) sumoylation

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Posttranslational modifications with ubiquitin and SUMO (small ubiquitin related modifier) are essential protein regulators involved in most cellular pathways. Ubiquitin and SUMO, themselves small proteins, are reversibly attached to their substrates depending on a tightly regulated enzymatic cascade. This involves the sequential action of a modifier specific E1 activating, E2 conjugating and E3 ligating enzyme for conjugation and specific enzymes for modifier specific deconjugation. Regulation is mainly performed at the level of E3 ligating and deconjugating enzymes, since these components ensure substrate specificity. Our work aims to gain insights into the consequences of E2 enzyme regulation which is expected to have widespread consequences on all downstream events, the cooperating E3 ligases and their substrates. In the proposed study we will investigate the biological consequences of regulating the ubiquitin conjugating enzyme E2-25K via sumoylation. Our recent biochemical findings indicated that upon sumoylation E2-25K switches its preference for E3 ligases. We now aim to study the consequences of E2-25K sumoylation in cell and mouse models by investigating the overall phenotype and also newly identified substrates.