An E2 Accessory Domain Increases Affinity for the Anaphase-promoting Complex and Ensures E2 Competition

The UBA domain of conjugating enzyme Ubc1/Ube2K facilitates assembly of K48/K63‐branched ubiquitin chains

“…However, growth of the Dubc4/UBC1-EA cells was strongly impaired in the presence of HU and at 37°C. Most likely, the deletion of UBC4 aggravates physiological disruptions caused by Ubc1-EA due to their partially overlapping cellular functions (Seufert et al, 1990;Medintz et al, 1998;Hiraishi et al, 2006;Girard et al, 2015). Our data suggest that ubiquitin binding by the UBA domain and thus branched chain formation by Ubc1 are not essential for vegetative growth of yeast cells but play an important role in the maintenance of cellular proteostasis in response to acute stress.…”

“…To verify the results of the proteomic analysis, we assessed the growth of the UBC1-EA strain in the presence of the DNA damaging agent hydroxyurea (HU) and at an elevated temperature of 37°C ( Fig 7F). Notably, the deletion of the UBC1 gene was shown to cause a growth defect and to be synthetically lethal with a UBC4 deletion (Seufert et al, 1990;Girard, et al, 2015). Moreover, expression of Ubc1-DUBA also does not yield viable cells in a Dubc4 background (Girard et al, 2015).…”

“…Notably, the deletion of the UBC1 gene was shown to cause a growth defect and to be synthetically lethal with a UBC4 deletion (Seufert et al, 1990;Girard, et al, 2015). Moreover, expression of Ubc1-DUBA also does not yield viable cells in a Dubc4 background (Girard et al, 2015). In this context, the UBA domain was suggested to mediate the recruitment of Ubc1 to the APC/C complex and to therefore fulfill essential functions during cell cycle progression.…”

Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)

“…In S. cerevisiae the APC/C generates canonical Lys48-linked chains also using two E2s: the initiating E2 Ubc4 and the elongating E2 Ubc1 [ 160 ]. A UBA domain in Ubc1 is required for processivity [ 160 ] by enhancing Ubc1 association with the APC/C in competition with Ubc4 [ 161 ].…”

Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination

“…To resolve this problem, it has been speculated that rapid reloading may occur through exclusive release of the catalytic UBC domain of UBE2S from APC2, while its C-terminal extension remains anchored on the APC/C platform (Brown et al, 2014). A conceptually similar mechanism was proposed for yeast UBC1, whose UBA domain may provide an APC/C anchor, allowing the catalytic domain to cycle between alternative interactions with the E1 and E3 (Girard et al, 2015). Although different in structural detail, these mechanisms are expected to enhance the residence time of a single chain-elongating E2 molecule on the E3 and render the system exquisitely sensitive to Lys +5 ubiquitination-mediated inhibition of E1-mediated reloading of this E2 molecule.…”