Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.2.19 (ubiquitin-protein ligase)
 799 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The SSY1 gene of Saccharomyces cerevisiae encodes a member of a large family of amino acid permeases. Compared to the 17 other proteins of this family, however, Ssy1p displays unusual structural features reminiscent of those distinguishing the Snf3p and Rgt2p glucose sensors from the other proteins of the sugar transporter family. We show here that SSY1 is required for transcriptional induction, in response to multiple amino acids, of the AGP1 gene encoding a low-affinity, broad-specificity amino acid permease. Total noninduction of the AGP1 gene in the ssy1Delta mutant is not due to impaired incorporation of inducing amino acids. Conversely, AGP1 is strongly induced by tryptophan in a mutant strain largely deficient in tryptophan uptake, but it remains unexpressed in a mutant that accumulates high levels of tryptophan endogenously. Induction of AGP1 requires Uga35p(Dal81p/DurLp), a transcription factor of the Cys6-Zn2 family previously shown to participate in several nitrogen induction pathways. Induction of AGP1 by amino acids also requires Grr1p, the F-box protein of the SCFGrr1 ubiquitin-protein ligase complex also required for transduction of the glucose signal generated by the Snf3p and Rgt2p glucose sensors. Systematic analysis of amino acid permease genes showed that Ssy1p is involved in transcriptional induction of at least five genes in addition to AGP1. Our results show that the amino acid permease homologue Ssy1p is a sensor of external amino acids, coupling availability of amino acids to transcriptional events. The essential role of Grr1p in this amino acid signaling pathway lends further support to the hypothesis that this protein participates in integrating nutrient availability with the cell cycle.
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PMID:Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-Box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease. 989 Oct 35

This is my reminiscent essay of my research life, but not a review article of specific subject. We found in the 1960s that BCAs (the branched chain amino acids, valine, leucine, and isoleucine) are unique in being the least metabolized amino acids in liver due to low activity of their transaminase. Later it was found clinically that BCAs are quite effective for recovery from hepatic encephalopathy. Furthermore, they could restore protein metabolism by stimulating synthesis and inhibiting degradation of body proteins under stress conditions. The signal of BCAs seems to be mediated by the amino acid sensor, Ssyl, which induces the amino acid permease AGP1. After liver injury, hepatocytes regenerate actively. In the 1980s, to study the molecular mechanism involved, we used primary cultured rat hepatocytes, the gene expressions of which respond very well to nutrients and hormones in the medium and to cell density. We identified HGF (hepatocyte growth factor) as a potent mitogen. The HGF receptor is cMet, an oncogene, and it initiates tyrosine phosphorylation in cellular signal transduction. The proteasome is a unique protease consisting of a very large multisubunit complex, which shows energy- and ubiquitin-dependent activity. In the 1990s we characterized the molecular structures of its subunits. Recently, proteasomes were found to degrade the HGF receptor, cMet. Furthermore, the Grrlp transcription factor, which is stimulated by Ssyl described above, has been identified as a ubiquitin-protein ligase. These studies on BCA, HGF, and proteasomes seemed to be unrelated to each other when I was working, but recent studies have shown that they are very closely related. So I would like to discuss the relations of my old work to recent findings.
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PMID:BCA, HGF, and proteasomes. 1060 2