The adenovirus E1A protein overrides the requirement for cellular ras in initiating DNA synthesis.
The adenovirus E1A protein overrides the requirement for cellular ras in initiating DNA synthesis.
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腺病毒 E1A 蛋白超越了细胞 ras 启动 DNA 合成的要求。
DOI：
10.1002/j.1460-2075.1994.tb06957.x
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Harter,ML
中科院分区：
文献类型：
--
作者：
Stacey,DW;Dobrowolski,SF;Piotrkowski,A;Harter,ML
腺病毒E1a蛋白可通过与细胞蛋白p300或pRb相互作用，诱导生长停滞细胞的DNA合成。此外，依赖血清和生长因子的细胞需要ras活性来启动DNA合成，最近我们发现，在显微注射抗ras抗体后，Balb/c 3T3细胞可以被阻断在G1早期或晚期。在本研究中，显微注射E1A243氨基酸蛋白不仅缩短了G0-S期的时间间隔，而且更重要的是，推翻了抗ras抗体在G1早期或晚期所产生的抑制作用。具体地说，无论E1a与抗ras共同注射到静止的细胞中，还是在血清刺激后18小时单独注射抗ras，它都能有效地诱导细胞中的DNA合成，否则细胞DNA合成将被阻断在G0/G1期。此外，注射不再与p300结合的突变形式的E1a在刺激ras活性已被抗ras中和的细胞中的DNA合成方面与野生型E1a一样有效。结果表明，E1a在促进细胞进入S期的过程中，能够抑制细胞内ras活性。此外，这些结果表明，pRb和/或pRb相关蛋白可能通过ras依赖的途径发挥作用，从而使E1a能够实现这一活性。
The adenovirus E1A protein can induce cellular DNA synthesis in growth‐arrested cells by interacting with the cellular protein p300 or pRb. In addition, serum‐ and growth factor‐dependent cells require ras activity to initiate DNA synthesis and recently we have shown that Balb/c 3T3 cells can be blocked in either early or late G1 following microinjection of an anti‐ras antibody. In this study, the E1A 243 amino acid protein is shown through microinjection not only to shorten the G0 to S phase interval but, what is more important, to override the inhibitory effects exerted by the anti‐ras antibody in either early or late G1. Specifically, whether E1A is co‐injected with anti‐ras into quiescent cells or injected 18 h following a separate injection of anti‐ras after serum stimulation, it efficiently induces cellular DNA synthesis in cells that would otherwise be blocked in G0/G1. Moreover, injection of a mutant form of E1A that can no longer associate with p300 is just as efficient as wild‐type E1A in stimulating DNA synthesis in cells whose ras activity has been neutralized by anti‐ras. The results presented here show that E1A is capable of overriding the requirement of cellular ras activity in promoting the entry of cells into S phase. Moreover, the results suggest the possibility that pRb and/or pRb‐related proteins may function in a ras‐dependent pathway that enables E1A to achieve this activity.