Disease relevance of MGA2

• The induction of YOL002c and YOL101c by toxic metal ion exposure is shown to be mediated by the Mga2p hypoxia sensor [1].

High impact information on MGA2

• SPT23 and MGA2 are relatives of mammalian NF-kappaB and control unsaturated fatty acid levels [2].
• Further analyses using low-oxygen response element (LORE)-CYC1-lacZ fusion reporter assays and electrophoretic mobility shift assays (EMSAs) demonstrated that MGA2 significantly affects the LORE-dependent hypoxic induction pathway of gene expression [3].
• When MGA2 was supplied by a plasmid, the LORE-dependent hypoxia-inducible reporter expression was recovered, as was the hypoxia-inducible complex in EMSAs in the S. cerevisiae Deltamga2 strain [3].
• Surprisingly, disruption of the MGA2 gene also reduces the half-life of the OLE1 transcript and abolishes fatty acid regulated instability [4].
• An analysis of mutants that are defective in mRNA degradation indicate that the Mga2p-requiring control mechanism that regulates the fatty acid-mediated instability of the OLE1 transcript acts by activating exosomal 3' --> 5'-exonuclease degradation activity [4].

Biological context of MGA2

• Our results suggest that Mga2p/Spt23p control cell viability by stimulating OLE1 transcription [5].
• These observations suggest that low-temperature and hypoxic signal transduction pathways share some components, and Mga2p is the first identified eukaryotic sensor for low temperature and oxygen [6].

Anatomical context of MGA2

• Regulation of unsaturated fatty acid biosynthesis in Saccharomyces: the endoplasmic reticulum membrane protein, Mga2p, a transcription activator of the OLE1 gene, regulates the stability of the OLE1 mRNA through exosome-mediated mechanisms [4].

Associations of MGA2 with chemical compounds

• Expressed alone, Mga2p induces high levels of OLE1 transcription in cells exposed to cobalt or grown in glycerol-containing medium [7].

Physical interactions of MGA2

• Taken together, our data indicate that the Npl4 complex may serve to target the proteasome to the ubiquitinated endoplasmic reticulum membrane-bound proteins Mga2p and Spt23p [8].
• Finally, we provide evidence that Mga2p90 and Mga2p120 dimerize and that Rsp5p binds heterodimeric Mga2p complexes both in vitro and in vivo [9].

Other interactions of MGA2

• MGA2 and SPT23 are modifiers of transcriptional silencing in yeast [10].
• Consistent with this proposal we find that deletion of MGA2 or SPT23 also suppresses the silencing defects caused by deletion of the SIR1 gene or by mutations in the HMR silencer sequences [10].

Analytical, diagnostic and therapeutic context of MGA2

• Data from Western blot assays provide evidence that under normoxic conditions, Mga2p processing produces approximately equimolar levels of the membrane-bound and processed forms and is unaffected by UFAs [11].

References