Disease relevance of NGG1

• A selection for yeast mutants resistant to GAL4-VP16-induced toxicity previously identified two genes, ADA2 and ADA3, which may function as adaptors for some transcriptional activation domains and thereby facilitate activation [1].

High impact information on NGG1

• We thus identified ADA1, ADA2, and ADA3 [2].
• Relief of glucose repression by NGG1 was dependent on the presence of GAL4, but was independent of the GAL4 promoter [3].
• We have cloned NGG1 by complementation and found that it contains an open reading frame of 2106 bp which could encode a protein with a molecular weight of 79,230 [3].
• In addition, NGG1p activity was seen for a promoter construct containing independent GAL4p binding sites [3].
• By a combination of mass spectrometry analysis and immunoblotting, we demonstrate that the adapter proteins Ada2, Ada3, and Gcn5 are indeed integral components of ADA [4].

Biological context of NGG1

• Transcriptional activation by yeast PDR1p is inhibited by its association with NGG1p/ADA3p [5].
• Deletion analysis of the his3-G25 promoter showed a correlation between the number of GAL4p binding sites and the relative level of NGG1p activity [3].
• The ADA3 gene is not absolutely essential for cell growth, but gene disruption mutants grow slowly and are temperature sensitive [6].
• ADA3 can be separated into two nonoverlapping domains, an amino-terminal domain and a carboxyl-terminal domain, which do not separately complement the slow-growth phenotype or transcriptional defect of a delta ada3 strain but together supply full complementation [7].
• Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation [8].

Associations of NGG1 with chemical compounds

• Characterization of NGG1, a novel yeast gene required for glucose repression of GAL4p-regulated transcription [3].
• Our results suggest that Ada2 potentiates the Gcn5 catalytic activity and that Ada3 facilitates nucleosomal acetylation and an expanded lysine specificity [8].
• Two of the genes, ADA3 and SPT7, are general transcriptional regulators; the third, YMR034c, is a putative sterol transporter [9].

Physical interactions of NGG1

• An overlapping region of the related transcriptional activator PDR3p was also found to interact with NGG1p [5].
• Further, ADA5 cofractionates and coprecipitates with ADA3 [10].
• The carboxyl-terminal domain of ADA3 alone suffices for heterotrimeric complex formation in vitro and activation of LexA-ADA2 in vivo [7].

Regulatory relationships of NGG1

• These results suggest that NGG1p acts to inhibit GAL4p function in glucose medium [3].
• This ability of ADA2 to activate transcription is mediated by ADA3, a gene with properties similar to ADA2 [11].

Other interactions of NGG1

• Amino acids 274-307 of NGG1p were required for interaction with PDR1p [5].
• Identification of native complexes containing the yeast coactivator/repressor proteins NGG1/ADA3 and ADA2 [12].
• This supports a role for NGG1p in the interaction with TBP and suggests that the interaction with TBP is functionally relevant [12].
• The additive effects of these mutations on binding of coactivator proteins correlated with their cumulative effects on transcriptional activation by Gcn4p in vivo, particularly with Ada3p, suggesting that recruitment of these coactivator complexes to the promoter is a cardinal function of the Gcn4p activation domain [13].
• We have identified Tra1p as a component of these complexes through tandem mass spectrometry analysis of proteins that associate with Ngg1p/Ada3p [14].

Analytical, diagnostic and therapeutic context of NGG1

• The presence of another high molecular mass complex was supported by the separation of one of the NGG1p- and ADA2p-containing peak fractions by gel-filtration chromatography [12].
• Immunoprecipitation analysis showed that the amino terminus of ADA2 was required for interaction with GCN5, while a region in the middle of ADA2 was necessary for interaction with ADA3 [15].
• Evidence for a direct role for NGG1p in regulating activator function is supported by the finding that NGG1p is also required for transcriptional activation by GAL4p-VPl6 and LexA-GCN4p (Pina, B., Berger, S. L., Marcus, G. A., Silverman, N., Agapite, J., and Guarente, L. (1993) Mol. Cell. Biol. 13, 5981-5989) [16].

References