ALG gene expression and cell cycle progression

The evolutionarily conserved ALG genes function in the dolichol pathway in the synthesis of the lipid-linked oligosaccharide precursor for protein N-g lycosylation. Increasing evidence suggests a role for these genes in the ce ll cycle. In Saccharomyces cerevisiae, coordinate regulation of the ALG gen es makes up the primary genomic response to growth stimulation; several fea tures of the ALG genes' expression resemble mammalian early growth response genes. However, only the first gene in the pathway, ALG7, is downregulated in response to an antimitogenic signal that leads to cell cycle arrest and differentiation, suggesting that selective inhibition of the first gene ma y be sufficient to regulate the dolichol pathway for the withdrawal from th e cell cycle. The availability of mutants in the early essential ALG genes has established functional relationships between these genes' expression an d G1/S transition, budding, progression through G2, and withdrawal from the cell cycle. Analysis of the regulation of ALG7 has provided insights into how this gene's expression is controlled at the molecular level. Recent stu dies have also begun to reveal how ALG7 expression is linked to cell cycle arrest in response to antimitogenic cues and have identified G1 cyclins as some of its downstream targets. Since the functions of the ALG genes appear to be as conserved among eukaryotes as the cell cycle machinery, it is lik ely that these genes play a similar role in mammalian cell proliferation an d differentiation. (C) 1999 Elsevier Science B.V. All rights reserved.