新的蛋白质调节重要的肿瘤抑制因子

PID蛋白调节P53减缓细胞生长的能力

纽约，2000年11月16日——哥伦比亚大学内科和外科医学院癌症遗传学研究所和病理学系的研究人员发现了一种名为PID的新蛋白，它是p53的一种新的细胞靶蛋白，p53是一种减慢组织生长的关键蛋白。因为提高p53的活性是许多抗肿瘤疗法的目标，这一发现可能有助于开发对抗癌症的新工具。病理学助理教授Gu Wei博士说:“PID明显抑制p53的功能。如果消除了PID的作用，就可以增强p53的功能。希望我们能够重新激活肿瘤细胞中的p53。”肿瘤抑制因子p53通常通过延缓细胞分裂和触发细胞死亡来降低细胞数量。在一个复杂的控制网络的节点上，p53对细胞生长的“刹车”又由几个不同的“开关”控制。一种调节p53活性的方法是通过乙酰基的化学连接，这被称为乙酰化，它使蛋白质更有效地打开基因，以减缓细胞分裂和加速细胞死亡。(1997年，顾博士第一个发现p53可以被乙酰化，并在功能上受到蛋白质乙酰化的调控。这一发现为乙酰化作为一种普遍的蛋白质修饰打开了一扇门，许多其他转录因子已经报道过)。 In the Nov. 16 issue of Nature, Dr. Gu, and researchers Jianyuan Luo, Fei Su, Delin Chen and Ariel Shiloh report finding PID (p53 target protein in the deacetylase complexes), which weakens p53’s grip on growth. PID trims down p53 acetylation, thus easing up on the p53 “brake.” By deacetylating p53, PID undermines p53’s ability to turn on genes that hinder progression of the cell cycle, thereby slowing cell division. It also keeps p53 from activating genes that initiate programmed cell death, or apoptosis. In this way, PID boosts cell proliferation and slows cell death. The accelerated growth that comes with diminished p53 function is a hallmark of cancers, and many tumors involve mutations in the p53 gene itself; others may involve binding of viral proteins to p53, or damage to either the downstream effectors of its function or some of the regulatory proteins that impinge on it. Identifying PID as a regulator of p53 activity might help explain the genetic basis of some tumors. “PID is overexpressed in certain cancers, such as breast cancers,” says Dr. Gu. Likewise, metastasis-associated protein 1, a protein similar to PID, was first discovered in metastatic cancer cells. PID may be a good target for anti-tumor drugs. Says Dr. Gu: “Inhibiting deacetylase activity has been a goal of a lot of anti-tumor therapies. But if you inhibit all deacetylases, you can harm normal cells too. By identifying a specific target, we can selectively enhance p53 activity to fight tumor growth without hurting normal cells.” The research was funded by the National Cancer Institute at the National Institutes of Health, the American Cancer Society, and the Herbert Irving Comprehensive Cancer Center at Columbia-Presbyterian Medical Center.

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