Disease relevance of UBC1

• Gankyrin is found in other complexes that contain Rb (retinoblastoma protein) and the ubiquitin protein ligase Mdm2 (murine double minute 2) [1].

High impact information on UBC1

• Here we show that Ubc1 acts as a further ubiquitin-conjugating enzyme in this pathway [2].
• Here, we demonstrate a novel activity of RAD6 protein--its ability to mediate protein degradation dependent on the N-end-recognizing ubiquitin protein ligase (E3) [3].
• All three mediate selective protein degradation, however, UBC1 appears to function primarily in the early stages of growth after germination of spores. ubc1 mutants generated by gene disruption display only a moderate slow growth phenotype, but are markedly impaired in growth following germination [4].
• This specific requirement for UBC1 after a state of quiescence suggests that degradation of certain proteins may be crucial at this transition point in the yeast life cycle [4].
• Such a high degree of similarity between the human E2(Mr = 17,000) and the yeast DNA repair enzyme is suggestive of important common structural constraints or roles in addition to ubiquitin carrier activity, since in yeast this function itself is not necessarily dependent on high conservation of primary structure [5].

Biological context of UBC1

• In the present work we report that the UBC1 enzyme assembles onto itself a multi-ubiquitin chain in vitro whose linkage configuration is dependent on the unconserved carboxyl-terminal extension or tail that is appended to its catalytic domain [6].
• Biochemical analysis of fructose-1,6-bisphosphatase import into vacuole import and degradation vesicles reveals a role for UBC1 in vesicle biogenesis [7].
• The ubiquitin molecule that anchors the chain is transferred to this lysine from the active site of the same UBC1 molecule [6].
• In order to probe the interface between these two proteins we have formed the covalent complex in situ (in the NMR tube) using Ub, the catalytic domain of UBC1, UBC1 delta450, an activation enzyme, E1, and Mg2+-ATP [8].
• The anaphase-promoting complex (APC) is a central regulator of the eukaryotic cell cycle and functions as an E3 ubiquitin protein ligase to catalyze the ubiquitination of a number of cell cycle regulatory proteins [9].

Associations of UBC1 with chemical compounds

• Loss of these functions was not shown to effect glucose-induced proteolysis of maltose permease, but loss of Ubc1, -4, and -5 was found to inhibit maltose permease expression at the post-transcriptional level [10].
• Assignment of the (1)H, (13)C and (15)N resonances of the class II E2 conjugating enzyme, Ubc1 [11].

Physical interactions of UBC1

• The ability of the Ubc1 to bind two ubiquitin molecules suggests that the UBA domain does not interact with the thioester-bound ubiquitin during polyubiquitin chain formation [12].

Other interactions of UBC1

• The products of yeast UBC4 and UBC5 genes along with that of UBC1 gene constitute a subfamily of functionally overlapping E2s that mediate the selective degradation of short-lived and abnormal proteins in vivo [13].
• Lower but significant activities of E3-CaM were observed when UBC1 replaced UBC4 [14].
• UBC1 encodes a novel member of an essential subfamily of yeast ubiquitin-conjugating enzymes involved in protein degradation [4].
• Moreover, the deletion of residues 103 to 114 within Cdc34, which are not present in the Ubc1-like E2s, allowed the S73K/S97D mutant to function as efficiently as wild-type Cdc34 protein [15].
• The similarity of this region with sequences contained within the tails of the UBC1 and UBC6 enzymes suggests that these tails may function in a similar manner [16].

Analytical, diagnostic and therapeutic context of UBC1

• The interaction of RFP-1 and UBC-1 was confirmed by co-immunoprecipitation experiments [17].

References