Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton
Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton
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法呢基转移酶抑制通过涉及肌动蛋白细胞骨架调节的复杂机制导致 ras 转化细胞的形态逆转
DOI：
10.1128/mcb.14.6.4193-4202.1994
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发表时间：
1994
影响因子：
5.3
通讯作者：
N. Kohl
中科院分区：
文献类型：
--
作者：
G. Prendergast;J. Davide;deSolms Sj;Giuliani Ea;S. Graham;J. Gibbs;I. OliffAllen;N. Kohl
法尼基蛋白转移酶的有效和特异性小分子抑制剂L-739，749可引起ras转化成纤维细胞（Rat 1/ras细胞）的快速形态逆转和生长抑制。在加入L-739，749后18 h内发生形态逆转。在不存在抑制剂的情况下，在转化的表型再次出现之前，回复的表型稳定数天。细胞扩大和肌动蛋白应力纤维的形成伴随着Rat 1/ras和正常Rat 1细胞的治疗。值得注意的是，Ras加工的抑制与回复表型的启动或维持无关。虽然用L-739，749单次处理足以在形态上逆转Rat 1/ras细胞，但需要重复抑制剂处理以显著降低细胞生长速率。因此，L-739，749对转化细胞形态和细胞骨架肌动蛋白组织的影响可以与对细胞生长的影响分开，这取决于暴露于法尼基蛋白转移酶抑制剂是短暂的还是重复的。相反，L-739，749对v-raf转化细胞的生长、形态或肌动蛋白组织没有影响。两者合计，结果表明，形态逆转的机制是复杂的，可能涉及法尼基化的蛋白质，控制组织的细胞骨架肌动蛋白。
A potent and specific small molecule inhibitor of farnesyl-protein transferase, L-739,749, caused rapid morphological reversion and growth inhibition of ras-transformed fibroblasts (Rat1/ras cells). Morphological reversion occurred within 18 h of L-739,749 addition. The reverted phenotype was stable for several days in the absence of inhibitor before the transformed phenotype reappeared. Cell enlargement and actin stress fiber formation accompanied treatment of both Rat1/ras and normal Rat1 cells. Significantly, inhibition of Ras processing did not correlate with the initiation or maintenance of the reverted phenotype. While a single treatment with L-739,749 was sufficient to morphologically revert Rat1/ras cells, repetitive inhibitor treatment was required to significantly reduce cell growth rate. Thus, the effects of L-739,749 on transformed cell morphology and cytoskeletal actin organization could be separated from effects on cell growth, depending on whether exposure to a farnesyl-protein transferase inhibitor was transient or repetitive. In contrast, L-739,749 had no effect on the growth, morphology, or actin organization of v-raf-transformed cells. Taken together, the results suggest that the mechanism of morphological reversion is complex and may involve farnesylated proteins that control the organization of cytoskeletal actin.
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通过气管内滴注逆转录病毒反义 K-ras 构建体来预防原位人肺癌生长。
影响因子：
11.2
作者：
Georges,RN;Mukhopadhyay,T;Zhang,Y;Yen,N;Roth,JA
通讯作者：
Roth,JA
DOI：
--
发表时间：
1992-07
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
R. Khosravi‐Far;A. Cox;K. Kato;C. Der
通讯作者：
R. Khosravi‐Far;A. Cox;K. Kato;C. Der
影响因子：
16.6
作者：
M. Barbacid
通讯作者：
M. Barbacid
DOI：
--
发表时间：
1991-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Pamela L. Crowell;R. Chang;Zhibin Ren;Charles E. Elson;Michael N. Gould
通讯作者：
Pamela L. Crowell;R. Chang;Zhibin Ren;Charles E. Elson;Michael N. Gould
DOI：
10.1073/pnas.89.14.6403
发表时间：
1992-07-15
影响因子：
11.1
作者：
KATO, K;COX, AD;DER, CJ
通讯作者：
DER, CJ