Disease relevance of LYS14

• To test the function of Lys14 as a transcriptional activator, this protein without its DNA-binding motif was fused to the DNA-binding domain of the Escherichia coli LexA protein [1].

High impact information on LYS14

• Importantly, wild-type Rsc4 bound an H3 tail peptide acetylated at Lys14, whereas a bromodomain mutant derivative did not [2].
• The product of the LYS14 gene of Saccharomyces cerevisiae activates the transcription of at least four genes involved in lysine biosynthesis [1].
• Deletion of this N-terminal portion including the cysteine-rich domain resulted in the loss of LYS14 function [1].
• The gene LYS14 was sequenced and, from its nucleotide sequence, predicted to encode a 790-amino-acid protein carrying a cysteine-rich DNA-binding motif of the Zn(II)2Cys6 type in its N-terminal portion [1].
• Repression of the genes for lysine biosynthesis in Saccharomyces cerevisiae is caused by limitation of Lys14-dependent transcriptional activation [1].

Biological context of LYS14

• In Saccharomyces cerevisiae, an intermediate of the lysine pathway, alpha-aminoadipate semialdehyde (alpha AASA), acts as a coinducer for the transcriptional activation of LYS genes by Lys14p [3].
• The point mutations abolishing the activation capacity of Lys14p are distributed all over the entire C-terminal segment [4].
• Analysis of LYS promoters and insertions within an heterologous reporter gene have allowed the characterization of an upstream activating element (UASLYS) able to confer Lys14- and alpha-amino-adipate semialdehyde-dependent activation as well as apparent repression by lysine to another yeast gene [5].
• In Saccharomyces cerevisae, feedback inhibition of homocitrate synthase isoenzymes by lysine modulates the activation of LYS gene expression by Lys14p [6].
• Taken together, Rsc4 bears essential tandem bromodomains that rely on H3 Lys14 acetylation to assist RSC complex for gene activation [2].

Anatomical context of LYS14

• Mistargeting of the peroxisomal lysine pathway to the cytosol increases the active concentration of aminoadipate semialdehyde, which is no longer contained in the peroxisome and can now activate Lys14p at much lower levels than in wild-type yeasts [7].

Associations of LYS14 with chemical compounds

• Two unlinked lysine genes (LYS9 and LYS14) are required for the synthesis of saccharopine reductase in Saccharomyces cerevisiae [8].
• Several enzymes of the lysine pathway of Saccharomyces cerevisiae were found to respond to an induction mechanism mediated by the product of gene LYS14 in the presence of 2-aminoadipate semialdehyde, an intermediate of this pathway [9].
• The synthesis of saccharopine dehydrogenase (glutamate-forming), previously shown to require the unlinked genes LYS9 and LYS14, is also affected by the induction mechanism [9].
• The expression of the structural genes for lysine (LYS) biosynthesis is controlled by a pathway-specific regulation mediated by the transcriptional activator Lys14 in the presence of alpha-aminoadipate semialdehyde, an intermediate of the pathway acting as a co-inducer [5].
• A nonameric core sequence is required upstream of the LYS genes of Saccharomyces cerevisiae for Lys14p-mediated activation and apparent repression by lysine [5].

Regulatory relationships of LYS14

• Furthermore, we show that the protein chaperone Hsp82p is required for full activation of LYS genes by the alphaAASA-activated Lys14p as well as by the constitutive Lys14p [4].

Other interactions of LYS14

• Genes LYS1, LYS9 and LYS14 have been cloned and their DNAs used to assay the corresponding messenger RNAs [9].
• The effects of lys80 mutations on LYS genes expression were dependent on the integrity of the activation system (Lys14p and alpha AASA) [3].
• Levels of these enzymes in lys2, lys14, and lys15 mutants were the same or lower than those in wild-type cells [10].
• In vitro, Hpa2 is able to acetylate specific lysine residues of histones H3 and H4 with a preference for Lys14 of histone H3 [11].

References