Disease relevance of TOM1

• Using a two-hybrid screening with TOM1, a putative ubiquitin-ligase gene of Saccharomyces cerevisiae, we isolated KRR1, a homologue of human HRB2 (for human immunodeficiency virus type 1 Rev-binding protein 2) [1].
• Most of the isolated tmr mutations rescued one of the defects seen in both types of heat stress response in the tom1 mutant [2].

High impact information on TOM1

• Endofin recruits TOM1 to endosomes [3].
• In addition, sucrose density gradient analysis showed that both TOM1 and endofin can be detected in cellular compartments marked by the early endosomal marker EEA1 [3].
• STO1 was isolated as a multicopy suppressor of TOM1, an uncharacterized mutation that leads to temperature-sensitive cell cycle arrest at the G2/M boundary [4].
• Strains with disruptions of both ngg1 and tom1 have the same phenotype as strains with a disruption of only ngg1 implying that these genes are acting through the same pathway [5].
• Moreover, the growth arrest of TOM1 mutants at elevated temperatures is partially suppressed by overexpression of RPS0A/B [6].

Biological context of TOM1

• Since overexpression of FPR4 does not suppress the reduced expression of the ARG1 promoter found in tom1 deletion strains, Tom1p probably has one or more functions beyond its involvement in gene expression [7].
• Yeast tom1 mutant exhibits pleiotropic defects in nuclear division, maintenance of nuclear structure and nucleocytoplasmic transport at high temperatures [8].
• Mutant alleles of the RPS0 and TOM1 genes have synergistic effects on cell growth at temperatures permissive for TOM1 mutants [6].
• The MSN2 gene, which encodes a zinc-finger transcription factor involved in the general stress response is also a multicopy suppressor of tom1 [2].
• A new gene (STM1; suppressor of tom1) of Saccharomyces cerevisiae was isolated by the ability to suppress the temperature sensitivity of a tom1 mutant, by increasing its gene dosage [9].

Anatomical context of TOM1

• Genes encoding ribosomal proteins Rps0A/B of Saccharomyces cerevisiae interact with TOM1 mutants defective in ribosome synthesis [6].

Regulatory relationships of TOM1

• FPR3 can also suppress the mating defect seen in tom1 strains [7].
• A high dose of the STM1 gene suppresses the temperature sensitivity of the tom1 and htr1 mutants in Saccharomyces cerevisiae [9].

Other interactions of TOM1

• The deletion of the TOM1 gene encoding a putative ubiquitin ligase causes a temperature sensitive cellular growth in Saccharomyces cerevisiae [10].
• We previously identified a zuo1 mutation as an extragenic suppressor of the tom1 mutant [10].
• Strains with mutant alleles of TOM1 are defective in multiple steps in rRNA processing, and interactions between RPS0A/B and TOM1 stem, in part, from their roles in the maturation of ribosomal subunits [6].

Analytical, diagnostic and therapeutic context of TOM1

• It also revealed the primarily cytosolic distribution of TOM1 in a variety of cell types by immunofluorescence analyses [3].

References