Gcn4

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Gcn4 is a transcription factor and a “master regulator” for gene expression which regulates close to one tenth of the yeast genome. In a study by Razaghi et al,[1] amino acid starvation activated the transcription factor Gcn4p, resulting in transcriptional induction of almost all genes involved in amino acid biosynthesis, including HIS4. Thus involvement of Gcn4 in regulation of both histidinol dehydrogenase HIS4 and interferon gamma hIFNγ was hypothesised as a scenario explaining the increased level of hIFNγ under amino acid starvation.[1]

Gcn4 is a highly conserved protein and its mammalian homolog is known as activating transcription factor-4 (ATF4).[2]

Overexpression of Gcn4 leads to the reduction in protein synthesis capacity which contributes to Gcn4-mediated increase of yeast lifespan[3]

In budding yeast, deletion of Gcn4 prevents HIS4 from targeting to the nuclear periphery upon transcriptional activation, indicating that Gcn4 is necessary for regulation of gene positioning and transcription.[4]

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  1. ^ a b Razaghi, Ali; Huerlimann, Roger; Owens, Leigh; Heimann, Kirsten (1 December 2015). "Increased expression and secretion of recombinant hIFNγ through amino acid starvation-induced selective pressure on the adjacent HIS4 gene in Pichia pastoris". Acta Facultatis Pharmaceuticae Universitatis Comenianae. 62 (2): 43–50. doi:10.1515/afpuc-2015-0031.
  2. ^ Murguía, J. R., & Serrano, R. (2012). New functions of protein kinase Gcn2 in yeast and mammals. IUBMB life, 64(12), 971-974. doi:10.1002/iub.1090 PMID 23129244
  3. ^ Nitish Mittal et al., & Mihaela Zavolan (2017). The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan. Nature Communications 8, Article number: 457 (2017) doi:10.1038/s41467-017-00539-y
  4. ^ Randise-Hinchliff, C., & Brickner, J. H. (2016). Transcription factors dynamically control the spatial organization of the yeast genome. Nucleus, 7(4), 369-374. doi:10.1080/19491034.2016.1212797