Mutations in the Lcb2p subunit of serine palmitoyltransferase eliminate the requirement for the TSC3 gene in Saccharomyces cerevisiae.
Mutations in the Lcb2p subunit of serine palmitoyltransferase eliminate the requirement for the TSC3 gene in Saccharomyces cerevisiae.
复制标题
丝氨酸棕榈酰转移酶 Lcb2p 亚基的突变消除了酿酒酵母对 TSC3 基因的需求。
DOI：
10.1002/yea.864
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Dunn,Teresa
中科院分区：
文献类型：
--
作者：
Monaghan,Erin;Gable,Ken;Dunn,Teresa
丝氨酸棕榈酰转移酶催化鞘脂合成中的关键步骤，即丝氨酸与棕榈酰辅酶A缩合形成3-酮二氢鞘氨醇。 Lcb1p 和 Lcb2p 两种蛋白质对于酶活性至关重要，而第三种蛋白质，80 个氨基酸的 Tsc3p，可数倍刺激丝氨酸棕榈酰转移酶的活性。 Tsc3p 与 Lcb1p-Lcb2p 复合物物理结合，并在翻译后刺激酶活性，但其确切功能尚不清楚。 Tsc3p 仅在高温下对细胞活力至关重要，尽管在 thetsc3Δ 突变体中丝氨酸棕榈酰转移酶活性降低，即使在允许的生长温度下也是如此。除了在 37°C 下刺激丝氨酸棕榈酰转移酶之外，显然 Tsc3p 不是任何重要过程所必需的，因为向生长培养基提供鞘氨醇碱会逆转 thetsc3Δ 突变体的温度敏感生长表型。为了进一步了解 Tsc3p 的功能，我们分离并表征了消除 Tsc3p 在 37°C 下生长所需的抑制突变体。这些研究表明，丝氨酸棕榈酰转移酶 Lcb2p 亚基的显性突变通过增加 Tsc3p 独立的丝氨酸棕榈酰转移酶活性来抑制 thetsc3Δ 无效突变体的温度敏感生长表型。版权所有 © 2002 约翰威利父子有限公司
Serine palmitoyltransferase catalyses the committed step in sphingolipid synthesis, the condensation of serine with palmitoyl‐CoA to form 3‐ketosphinganine. Two proteins, Lcb1p and Lcb2p, are essential for enzyme activity and a third protein, the 80‐amino acid Tsc3p, stimulates the activity of serine palmitoyltransferase several‐fold. Tsc3p physically associates with a complex of Lcb1p–Lcb2p and stimulates enzyme activity post‐translationally, but its precise function is not known. Tsc3p is essential for cell viability only at elevated temperatures, although serine palmitoyltransferase activity is reduced in thetsc3Δ mutant, even at permissive growth temperatures. Tsc3p is apparently not required for any essential process besides stimulation of serine palmitoyltransferase at 37°C, since providing sphingoid bases to the growth medium reverses the temperature‐sensitive growth phenotype of thetsc3Δ mutant. To gain further insight into the function of Tsc3p, suppressor mutants that eliminate the Tsc3p requirement for growth at 37°C were isolated and characterized. These studies show that dominant mutations in the Lcb2p subunit of serine palmitoyltransferase suppress the temperature‐sensitive growth phenotype of thetsc3Δ null mutant by increasing the Tsc3p‐independent serine palmitoyltransferase activity. Copyright © 2002 John Wiley & Sons, Ltd.