Protein synthesis and degradation in cultured muscle is altered by a phorbol diester tumor promoter.
Protein synthesis and degradation in cultured muscle is altered by a phorbol diester tumor promoter.
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佛波二酯肿瘤促进剂可以改变培养肌肉中的蛋白质合成和降解。
DOI：
10.1016/0003-9861(82)90164-3
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发表时间：
1982
影响因子：
3.9
通讯作者：
Holtzer,H
中科院分区：
文献类型：
--
作者：
West,CM;Holtzer,H
研究了肿瘤启动子12- o - tetradecanoylphorbol13 -acetate （TPA）对培养鸡胚肌管中几种多肽合成和降解的相对速率的影响。影响的方向部分与多肽是仅在肌管中表达还是也在其增殖前体中表达有关。8种肌管特有多肽的合成除1种外均受到抑制，除2种外均受到刺激。例外是中间丝亚基。相反，几种非肌管特有多肽的代谢要么不受影响，要么受到相反方向的影响。一种用细胞外放射性亮氨酸使细胞内亮氨酸前体池饱和的方法表明，蛋白质合成的绝对速率如果受到启动子的影响，则只有最低限度的影响。在去除启动子后，对蛋白质合成的影响至少部分可逆。合成和降解的变化并没有反映培养肌管的正常成熟变化，因此它们似乎是由TPA诱导的。数据表明，在某些情况下，几种蛋白质的合成和降解率在肌管中是负耦合的。它们也为早期的超微结构观察提供了部分解释，即TPA导致肌丝的丢失和中间丝的积累。由于肌管处于细胞周期的G1（或G0）阶段，并且培养物的DNA含量不受TPA的影响，因此TPA的作用不是通过细胞周期依赖机制介导的。
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was observed to influence the relative rates of synthesis and degradation of several polypeptides in cultured chick embryo myotubes. The direction of influence partially correlated with whether the polypeptide was uniquely expressed in myotubes or also expressed in its proliferating precursors. The synthesis of all but one of the eight myotube-unique polypeptides examined was inhibited and the degradation of all but two was stimulated. The exceptions were intermediate filament subunits. In contrast, the metabolism of several non-myotube-unique polypeptides was either unaffected or influenced in the opposite direction. A method involving saturation of the intracellular leucine precursor pool with extracellular radioactive leucine suggested that the absolute rate of protein synthesis was only minimally, if at all, affected by the promoter. The effects on protein synthesis were at least partially reversible following removal of the promoter. The changes in synthesis and degradation did not reflect normal maturational changes in cultured myotubes and thus they appeared to be induced by TPA. The data suggest that under some circumstances the rates of synthesis and degradation of several proteins are inversely coupled in the myotube. They also provide a partial explanation for earlier ultrastructural observations that TPA caused a loss of myofilaments and an accumulation of intermediate filaments. Since myotubes occupy the G1(or G0) stage of the cell cycle, and the DNA content of the cultures was not affected by TPA, TPA's effects were not mediated through cell cycle-dependent mechanisms.