COP10 is a ubiquitin-conjugating enzyme variant (UEV), which is thought to act together with COP1, DET1, and the COP9 signalosome (CSN) in Arabidopsis to repress photomorphogenesis. Here, we demonstrate that COP10 interacts with ubiquitin-conjugating enzymes (E2s) in vivo, and can enhance their activity in vitro, an activity distinct from previous characterized UEVs such as MMS2 and UEV1. Furth...

Efforts to develop inhibitors, activators, and effectors of biological reactions using small molecule libraries are often hampered by interference compounds, artifacts, and false positives that permeate the pool of initial hits. Here, we report the discovery of a promising initial hit compound targeting the Fanconi anemia ubiquitin-conjugating enzyme Ube2T and describe its biophysical and bioch...

The targeting of proteolytic substrates is accomplished by a family of ubiquitin-conjugating (E2) enzymes and a diverse set of substrate recognition (E3) factors. The ligation of a multiubiquitin chain to a substrate can promote its degradation by the proteasome. However, the mechanism that facilitates the translocation of a substrate to the proteasome in vivo is poorly understood. We have disc...

Depletion of specific cellular proteins is a powerful tool in biological research and has many medical and agricultural benefits. In contrast to genetic methods currently available to attenuate protein levels, we describe an alternative approach that redirects the ubiquitin-dependent proteolytic pathway to facilitate specific proteolytic removal. Degradation via the ubiquitin pathway requires t...

Proinflammatory cytokines, such as interleukin-1 beta (IL-1β), are important mediators of psoriasis. Ubiquitin conjugating enzyme E2 L3 (UBE2L3), an enzyme, is thought to be indirect target IL-1β secretion by binding ubiquitin ligases (E3s) tripartite motif-containing protein 21 (TRIM21). However, its role in the psoriasis remains unknown. In this study, we found that UBE2L3 expression was decr...

PURPOSE Dysfunction of the ubiquitin-proteasome pathway (UPP) is associated with several age-related degenerative diseases. The objective of this study was to investigate the effect of oxidative stress on the UPP in cultured human retina pigment epithelial cells. METHODS To mimic physiological oxidative stress, ARPE-19 cells were exposed to continuously generated H2O(2) or A2E-mediated photoo...

Histone proteins are subject to modifications, such as acetylation, methylation, phosphorylation, ubiquitination, glycosylation, and ADP ribosylation, some of which are known to play important roles in the regulation of chromatin structure and function. Here we report that histone H4 is modified by small ubiquitin-related modifier (SUMO) family proteins both in vivo and in vitro. H4 binds to th...