The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer - Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2
The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer - Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2
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DOI：
10.1074/jbc.m110568200
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发表时间：
2002-04-12
影响因子：
4.8
通讯作者：
Hsieh, JT
中科院分区：
文献类型：
--
作者：
Wang, Z;Tseng, CP;Hsieh, JT
DOC-2/DAB 2是具有抑瘤活性的失能基因家族成员。它的下调与几种肿瘤有关，其N末端的丝氨酸磷酸化调节DOC-2/DAB 2对AP-1转录活性的抑制作用。我们描述了DIP 1/2的克隆，DIP 1/2是一个与DOC-2/DAB 2的N-末端结构域相互作用的新基因。DIP 1/2是一种新的GTP酶激活蛋白，含有一个Ras GTP酶激活蛋白同源结构域（N端）和另外两个独特的结构域（即10个脯氨酸重复序列和亮氨酸拉链）。DOC-2/DAB 2和DIP 1/2之间的相互作用在正常组织如脑和前列腺中检测到。这两种蛋白质的表达改变通常在前列腺癌细胞中检测到。事实上，DIP 1/2的存在有效地阻断了促分裂原诱导的基因表达，并抑制了前列腺癌的生长。因此，DOC-2/DAB 2和DIP 1/2似乎代表了维持细胞稳态的独特负调控复合物。
DOC-2/DAB2 is a member of the disable gene family with tumor-inhibitory activity. Its down-regulation is associated with several neoplasms, and serine phosphorylation of its N terminus modulates DOC-2/DAB2's inhibitory effect on AP-1 transcriptional activity. We describe the cloning of DIP1/2, a novel gene that interacts with the N-terminal domain of DOC-2/DAB2. DIP1/2 is a novel GTPase-activating protein containing a Ras GTPase-activating protein homology domain (N terminus) and two other unique domains (i.e. 10 proline repeats and leucine zipper). Interaction between DOC-2/DAB2 and DIP1/2 is detected in normal tissues such as the brain and prostate. Altered expression of these two proteins is often detected in prostate cancer cells. Indeed, the presence of DIP1/2 effectively blocks mitogen-induced gene expression and inhibits the growth of prostate cancer. Thus, DOC-2/DAB2 and DIP1/2 appear to represent a unique negative regulatory complex that maintains cell homeostasis.