Erg28, also known as chromosome 14 open reading frame 1 (C14orf1), is a gene conserved from yeast to humans. It plays a role in sterol biosynthesis pathways, with its encoded protein potentially acting as a scaffold in the sterol C-4 demethylation complex [3,4,6]. In plants, it is involved in preventing the accumulation of a sterol biosynthetic intermediate that interferes with polar auxin transport [2]. In mammals, it is implicated in cholesterol synthesis, a process crucial for various cellular functions [1].

In mammalian studies, Huh7 ERG28-KO cell lines showed reduced total cholesterol levels in sterol-depleted environments and a 60-75% reduction in the rate of cholesterol synthesis compared to wild-type cells. The activation of SREBP-2 was also impaired in ERG28-KO cells under sterol-replete conditions, although the mechanism remains unclear [1]. In yeast, disruption of the ERG28 gene led to slow growth and accumulation of sterol intermediates [4,6]. Additionally, in Agrobacterium-mediated yeast transformation, the erg28Δ mutant showed low transformation efficiency, suggesting ERG28 may contribute by sensing a congested environment [5].

In conclusion, Erg28 is essential for sterol biosynthesis in multiple organisms. In mammals, its role in cholesterol synthesis is significant, and gene knockout studies in cell lines and yeast have provided insights into its function. Understanding Erg28 could potentially inform therapeutic strategies for diseases associated with aberrant cholesterol metabolism [1].

References:

1. Capell-Hattam, Isabelle M, Fenton, Nicole M, Coates, Hudson W, Sharpe, Laura J, Brown, Andrew J. 2022. The Non Catalytic Protein ERG28 has a Functional Role in Cholesterol Synthesis and is Coregulated Transcriptionally. In Journal of lipid research, 63, 100295. doi:10.1016/j.jlr.2022.100295. https://pubmed.ncbi.nlm.nih.gov/36216146/

2. Mialoundama, Alexis Samba, Jadid, Nurul, Brunel, Julien, Camara, Bilal, Bouvier, Florence. 2013. Arabidopsis ERG28 tethers the sterol C4-demethylation complex to prevent accumulation of a biosynthetic intermediate that interferes with polar auxin transport. In The Plant cell, 25, 4879-93. doi:10.1105/tpc.113.115576. https://pubmed.ncbi.nlm.nih.gov/24326590/

3. Mo, Caiqing, Valachovic, Martin, Bard, Martin. . The ERG28-encoded protein, Erg28p, interacts with both the sterol C-4 demethylation enzyme complex as well as the late biosynthetic protein, the C-24 sterol methyltransferase (Erg6p). In Biochimica et biophysica acta, 1686, 30-6. doi:. https://pubmed.ncbi.nlm.nih.gov/15522820/

4. Mo, C, Valachovic, M, Randall, S K, Nickels, J T, Bard, M. 2002. Protein-protein interactions among C-4 demethylation enzymes involved in yeast sterol biosynthesis. In Proceedings of the National Academy of Sciences of the United States of America, 99, 9739-44. doi:. https://pubmed.ncbi.nlm.nih.gov/12119386/

5. Ohmine, Yuta, Satoh, Yukari, Kiyokawa, Kazuya, Moriguchi, Kazuki, Suzuki, Katsunori. 2016. DNA repair genes RAD52 and SRS2, a cell wall synthesis regulator gene SMI1, and the membrane sterol synthesis scaffold gene ERG28 are important in efficient Agrobacterium-mediated yeast transformation with chromosomal T-DNA. In BMC microbiology, 16, 58. doi:10.1186/s12866-016-0672-0. https://pubmed.ncbi.nlm.nih.gov/27038795/

6. Gachotte, D, Eckstein, J, Barbuch, R, Roberts, C, Bard, M. . A novel gene conserved from yeast to humans is involved in sterol biosynthesis. In Journal of lipid research, 42, 150-4. doi:. https://pubmed.ncbi.nlm.nih.gov/11160377/