Disease relevance of UMP1

• Cells lacking Ump1p exhibit a lack of coordination between the processing of beta subunits and proteasome assembly, resulting in functionally impaired proteasomes [1].

High impact information on UMP1

• Here we present a model proposing that (1) Nob1p serves as a chaperone to join the 20S proteasome with the 19S regulatory particle in the nucleus and facilitates the maturation of the 20S proteasome and degradation of Ump1p, and (2) Nob1p is then internalized into the 26S proteasome and degraded to complete 26S proteasome biogenesis [2].
• Ume3p destruction in response to oxidative stress, but not to ethanol treatment, requires DOA4 and UMP1, two factors required for 26S proteasome activity [3].
• The deletion of 19 residues from the beta7/Pre4 C terminus leads to an accumulation of half-proteasome precursor complexes containing the maturation factor Ump1 [4].
• We show that UMP1 is not epistatic to RAD23 and RAD2, which are involved in the nucleotide excision repair (NER) pathway [5].
• To elucidate the origin of these DNA repair phenotypes of the proteasomal mutants, we performed epistasis analysis, with respect to UV sensitivity, using yeast strains with the UMP1 deletion in different DNA repair backgrounds [5].

Biological context of UMP1

• Expression of UMP1 is inducible by DNA damage and required for resistance of S. cerevisiae cells to UV light [6].
• Deletion of UMP1, a gene necessary for 20S proteasome biogenesis, had no effect on cellular viability under normal growth conditions, but impaired the ability of cells to survive under stationary phase conditions [7].
• RNA interference toward UMP1 induces proteasome inhibition in Saccharomyces cerevisiae: evidence for protein oxidation and autophagic cell death [8].
• Deletion of UBI4 partially suppressed the growth defects of ump1 mutants, indicating that accumulation of polyubiquitylated proteins is deleterious to cell growth [9].
• For U. maydis, disruption of ump2 eliminated the filamentous phenotype of haploid cells on low ammonium, while ump1 disruption only slightly reduced methylamine uptake [10].

Anatomical context of UMP1

• The complex biogenesis is tightly regulated which requires additional components such as the maturation factor Ump1/POMP, an ubiquitous protein in eukaryotic cells [11].

Associations of UMP1 with chemical compounds

• MMS induction of UMP1 expression occurs at the transcriptional level and is independent of the activity of the regulatory checkpoint kinases encoded by MEC1 [6].
• It is also shown that the disruption of UMP1 causes increased sensitivity of yeast cells to killing by UV radiation, but only slight sensitivity to HU treatment, and does not cause any increase in the killing effect of MMS [6].
• We observed that Saccharomyces cerevisiae transformed to express increased levels of Ump1 exhibited increased viability in response to a variety of oxidative stressors (menadione, hydrogen peroxide, 4-hydroxynonenal) [12].

Other interactions of UMP1

• We identified the genes mutated in three of the rns mutants, rns1, rns2, and rns3, as DSL1, UMP1, and SEC17, respectively [13].
• We have identified Blm3, a conserved nuclear protein, as a new component of Ump1-associated precursor complexes [14].
• Subsequently, rns (ribonuclease T1 sensitive) mutants with mutations in the rns1 (DSL1), rns2 (UMP1), and rns3 (SEC17) genes, were identified [15].
• These assays additionally implicated three proteins, Bim1, Ump1, and YKL171W, in proteasome function [16].

References