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Albumin promotes the progression of fibroblasts through late G1 into S-phase in the absence of growth factors.
Cell Cycle ( IF 3.4 ) Pub Date : 2020-07-26 , DOI: 10.1080/15384101.2020.1795999
Sharmeen Uddin 1, 2 , Nataliya Melnyk 1 , David A Foster 1, 2, 3, 4
Affiliation  

G1 cell cycle progression is controlled largely by growth factors in early G1 indicating that it is appropriate to divide and by nutrients in late G1 indicating sufficient raw material for cell division. We previously mapped a late G1 cell cycle checkpoint for lipids upstream from a mammalian target of rapamycin complex 1 (mTORC1)-mediated checkpoint and downstream from a mid-G1 checkpoint known as the Restriction point. We therefore investigated a role for lipids in progression through late G1 into S-phase. Quiescent BJ-hTERT human fibroblasts were primed with 10% fetal bovine serum (FBS) for 3.5 h at which time, cells were treated with a mixture of lipids and carrier bovine serum albumin (BSA) along with [3 H]-thymidine deoxyribose ([3 H]-TdR) to monitor progression into S-phase. Surprisingly, BSA by itself was more effective than FBS in promoting progression to S-phase – the lipids had no impact on progression. While insulin strongly stimulated mTORC1 activity, it did not impact on [3 H]-TdR incorporation. Although BSA modestly elevated mTORC1 activity, rapamycin strongly inhibited BSA-induced progression to S-phase. BSA treatment promoted mitosis, but not progression through a second G1. Thus, after priming quiescent cells with FBS, albumin was sufficient to promote progression into S-phase. The BSA was not simply a source of amino acids in that amino acids were present in the culture media. We propose that the presence of albumin – the most abundant protein in serum – reflects a broader availability of essential amino acids needed for cell growth.



中文翻译:

在没有生长因子的情况下,白蛋白促进成纤维细胞从 G1 晚期进入 S 期。

G 1细胞周期进程在很大程度上受早期 G 1 中的生长因子控制,表明它适合分裂,而晚期 G 1 中的营养物质表明细胞分裂有足够的原材料。我们之前在哺乳动物雷帕霉素复合物 1 靶标 (mTORC1) 介导的检查点上游和称为限制点的 G 1中期检查点下游绘制了脂质的晚期 G 1细胞周期检查点。因此,我们研究了脂质在 G 1晚期进展中的作用进入 S 相。静止的 BJ-hTERT 人成纤维细胞用 10% 胎牛血清 (FBS) 引发 3.5 小时,然后用脂质和载体牛血清白蛋白 (BSA) 以及 [ 3  H]-胸苷脱氧核糖的混合物处理细胞。[ 3  H]-TdR) 以监测进入 S 期的进展。令人惊讶的是,BSA 本身在促进 S 期进展方面比 FBS 更有效——脂质对进展没有影响。虽然胰岛素强烈刺激 mTORC1 活性,但它不影响 [ 3  H]-TdR 掺入。尽管 BSA 适度提高了 mTORC1 活性,但雷帕霉素强烈抑制 BSA 诱导的 S 期进展。BSA 治疗促进有丝分裂,但不会通过第二个 G 1进行进展. 因此,在用 FBS 启动静止细胞后,白蛋白足以促进进入 S 期。BSA 不仅仅是氨基酸的来源,因为氨基酸存在于培养基中。我们认为,血清中最丰富的蛋白质白蛋白的存在反映了细胞生长所需的必需氨基酸的更广泛可用性。

更新日期:2020-09-08
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