Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human.

By J. C. Jiang, P. Kirchman, M. Zagulski, J. Hunt, S. Jazwinski. 1998

LAG1 is a longevity gene, the first such gene to be identified and cloned from the yeast Saccharomyces cerevisiae. A close homolog of this gene, which we call LAC1, has been found in the yeast genome. We have cloned the human homolog of LAG1 with the ultimate goal of examining its possible function in human aging. In the process, we have also cloned a homolog from the nematode worm Caenorhabditis elegans. Both of these homologs, LAG1Hs and LAG1Ce-1, functionally complemented the lethality of a lag1delta lac1delta double deletion, despite low overall sequence similarity to the yeast proteins. The proteins shared a short sequence, the Lag1 motif, and a similar transmembrane domain profile. Another, more distant human homolog, TRAM, which lacks this motif, did not complement. LAG1Hs also restored the life span of the double deletion, demonstrating that it functions in establishing the longevity phenotype in yeast. LAG1Hs mapped to 19p12, and it was expressed in only three tissues: brain, skeletal muscle, and testis. This gene possesses a trinucleotide (CTG) repeat within exon 1. This and its expression profile raise the possibility that it may be involved in neurodegenerative disease. This possibility suggests at least one way in which LAG1Hs might be involved in human aging.

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Citations in the corpus

Mammalian Ceramide Synthases (2010, background): “Subsequent bioinformatics analyses (13, 17, 18) revealed additional mammalian Lag homologs, originally characterized as translocating chain-associating membrane protein homologs (TRH) (8, 10), with the ceramides synthesized”
Molecular Cloning, Characterisation and Tissue-specific Expression of Human LAG3, a Member of the Novel Lag1 Protein Family (2003, background): “The results indicated that, the LAG3Hs had an expression pattern different from that of LAG1Hs, which was expressed at high levels in limited tissues, including human brain, skeletal muscle and testis (Jiang et al., 1998).”
Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae. (2001, background): “Sequence homologues of LAG1 and LAC1 were found in numerous eukaryotes including humans (Jiang et al., 1998; Brandwagt et al., 2000), but nothing is known about the molecular function of the encoded proteins.”
Lip1p: a novel subunit of acyl‐CoA ceramide synthase (2005, background): “Homologs have been found in a wide variety of eukaryotes (Jiang et al, 1998; Brandwagt et al, 2000).”
Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas (2007, background): “The mammalian homologues of yeast LAG1 were later identified in human, Caenorhabditis elegans (19), and mouse (17), and recent independent studies have shown specific functions of mouse LASS1, LASS5, and LASS6 in the specific generation of C18-, C16- and C14/C16ceramides, respectively (17, 30, 31).”