SIGNALING OF APOPTOSIS DURING CELL TRANSFORMATION

工作总结：正常的生物体内平衡是通过一种 小心平衡细胞增殖和细胞死亡过程。 癌 细胞在迅速分裂和扩张的同时，也可能经历 细胞死亡 了解癌细胞是如何死亡或丧失的是很重要的 它们对细胞死亡过程的敏感性。 我们已经证明， 在肿瘤过程的各个阶段，细胞对 经历细胞凋亡不同。 在单独的研究中，我们正在追求 凋亡途径对氧化损伤的反应。 在以下研究中， p53在这一过程中的作用， 我们发现凋亡也 似乎需要p85激酶。此外，我们还发现Rb 蛋白质可能是细胞决定是否停止或 受伤后自杀。此外，我们也在研究 EIA结合，p300蛋白，作为多重整合的作用， 细胞反应。 我们发现p300可以与c-fos结合， 蛋白质在细胞应激条件下导致细胞凋亡。的 c-fos的升高已被证明是低血清诱导的 仓鼠成纤维细胞凋亡。我们认为c-fos与 p300对于细胞决定经历细胞死亡是至关重要的。

Summary of Work: Normal organismal homeostasis is maintained through a careful balance of cell proliferation and cell death processes. Cancer cells, while rapidly undergoing division and expansion, may also undergo cell death. It is important to understand how cancer cells die or lose their susceptibility to the cell death process. We have shown that the susceptibility of cells at various stages of the neoplastic process to undergo apoptosis differs. In separate studies, we are pursuing the apoptotic pathway in response to oxidative damage. In studies following the role of p53 in this process, we have found that apoptosis also appears to require the p85 kinase. In addition we have found that the Rb protein may be a key player in the cellular decision whether to arrest or commit suicide following injury. In addition, we have also been examining the role of the EIA binding, p300 protein, as an integrator of multiple cellular responses. We have found that p300 can couple with the c-fos protein under conditions of cellular stress that result in apoptosis. The elevation of c-fos has been shown to be a key event in low serum induced apoptosis of hamster fibroblasts. We propose that the binding of c-fos to p300 is critical for the cellular decision to undergo cell death.