Cloning and characterization of the human activity-dependent neuroprotective protein
Cloning and characterization of the human activity-dependent neuroprotective protein
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DOI：
10.1074/jbc.m007416200
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发表时间：
2001-01-05
影响因子：
4.8
通讯作者：
Gozes, I
中科院分区：
文献类型：
--
作者：
Zamostiano, R;Pinhasov, A;Gozes, I
我们最近克隆了小鼠活动依赖性神经保护蛋白（ADNP）。在此，我们公开了从胎脑cDNA文库中克隆人ADNP（hADNP）。这两个ADNP直系同源物的比较序列分析表明在mRNA水平上90%的同一性。发现了几个单核苷酸多态性位点。推导的蛋白质结构包含九个锌指，脯氨酸丰富的区域，核二分定位信号，和同源框结构域的配置文件，表明转录因子的功能。进一步的比较分析确定了一个ADNP parasites（33%的同一性和46%的相似性），表明这些基因属于一个新的蛋白质家族，具有9个锌指基序，随后是一个同源框结构域。hADNP基因结构跨度类似于40个外显子，包括5个外显子和4个内含子，其中第二个外显子为非翻译的选择性剪接。hADNP基因定位于染色体20 q12 -13.2，这是一个与侵袭性肿瘤生长相关的区域，在许多肿瘤中经常扩增，包括乳腺癌、膀胱癌、卵巢癌、胰腺癌和结肠癌，hADNP mRNA在不同的正常组织中大量表达，并且在恶性细胞中高表达水平。反义寡核苷酸下调ADNP可上调肿瘤抑制因子p53，并使肠癌细胞的存活率降低90%。因此，ADNP可能通过调节p53参与维持细胞存活。
We have recently cloned the mouse activity-dependent neuroprotective protein (ADNP). Here, we disclose the cloning of human ADNP (hADNP) from a fetal brain cDNA library. Comparative sequence analysis of these two ADNP orthologs indicated 90% identity at the mRNA level. Several single nucleotide polymorphic sites were noticed. The deduced protein structure contained nine zinc fingers, a proline-rich region, a nuclear bipartite localization signal, and a homeobox domain profile, suggesting a transcription factor function. Further comparative analysis identified an ADNP paralog (33% identity and 46% similarity), indicating that these genes belong to a novel protein family with a nine-zinc finger motif followed by a homeobox domain. The hADNP gene structure spans similar to 40 kilobases and includes five exons and four introns with alternative splicing of an untranslated second exon. The hADNP gene was mapped to chromosome 20q12-13.2, a region associated with aggressive tumor growth, frequently amplified in many neoplasias, including breast, bladder, ovarian, pancreatic, and colon cancers, hADNP mRNA is abundantly expressed in distinct normal tissues, and high expression levels were encountered in malignant cells. Down-regulation of ADNP by antisense oligodeoxynucleotides up-regulated the tumor suppressor p53 and reduced the viability of intestinal cancer cells by 90%. Thus, ADNP is implicated in maintaining cell survival, perhaps through modulation of p53.