文章：

ASPP和癌症

ASPPs and cancer

原文发布日期：2006-02-16

DOI: 10.1038/nrc1818

类型: Review Article

开放获取: 否

要点：

1. The p53-dependent apoptotic pathway is central to tumour prevention and is consistently disrupted in malignancy; disruption can occur in p53 itself or in any of its cofactors or target genes.
2. The members of the ASPP (ankyrin-repeat-, SH3-domain- and proline-rich-region-containing protein) family have been identified as specific regulators of p53-, p63- and p73-mediated apoptosis. The family comprises three members of which two, ASPP1 and ASPP2, are pro-apoptotic and the third, inhibitory iASPP (iASPP), is anti-apoptotic. The importance of the ASPP family in regulating p53 function is supported by the genetic evidence that C. elegans iASPP is an inhibitor of p53 and can also inhibit the function of human p53 in human cells as effectively as humn iASPP.
3. The ASPP family is characterized by a highly conserved carboxyl terminus — ankryin repeats, SH3 (Src homology 3) domain and proline-rich region — which is the preferred binding site for its partners, including the tumour suppressor p53, BCL2, RELA/p65, protein phosphatase 1, YES-associated protein and adenomatosis polyposis coli 2. The amino terminus is conserved only in the pro-apoptotic members, ASPP1 and ASPP2.
4. ASPP expression levels correlate with cellular sensitivity (ASPP1 and ASPP2 increase sensitivity) and resistance (iASPP increases resistance) to apoptosis. Deregulation of ASPP expression has been reported in several different cancers, underlining their importance in tumour development. The members of the ASPP family might be new molecular targets for cancer therapy.

要点翻译：

1. p53依赖性凋亡通路是肿瘤预防的核心，且在恶性肿瘤中持续失调；该失调可发生于p53本身或其任何辅因子或靶基因。
2. ASPP家族（包含锚蛋白重复序列、SH3结构域和富含脯氨酸区域的蛋白质）成员已被确定为p53、p63和p73介导凋亡的特异性调节因子。该家族包含三个成员，其中ASPP1和ASPP2促凋亡，第三个抑制性成员iASPP则抗凋亡。ASPP家族在调控p53功能中的重要性得到遗传学证据支持：线虫iASPP是p53的抑制剂，并能像人iASPP一样有效抑制人类细胞中人p53的功能。
3. ASPP家族的特征是其高度保守的羧基末端——锚蛋白重复序列、SH3结构域和富含脯氨酸区域——这是其相互作用蛋白（包括抑癌蛋白p53、BCL2、RELA/p65、蛋白磷酸酶1、YES相关蛋白和结肠腺瘤性息肉病蛋白2）的首选结合位点。氨基末端仅在促凋亡成员ASPP1和ASPP2中保守。
4. ASPP表达水平与细胞对凋亡的敏感性（ASPP1和ASPP2增强敏感性）和耐药性（iASPP增强耐药性）相关。多种癌症中均报道了ASPP表达的失调，凸显了其在肿瘤发展中的重要性。ASPP家族成员可能成为癌症治疗的新分子靶点。

英文摘要：

One of the most frequently mutated genes in human cancers, tumour suppressor p53 (TP53), can induce cell-cycle arrest and apoptosis. The apoptotic function of p53 is tightly linked to its tumour-suppression function and the efficacy of many cancer therapies depends on this. The identification of a new family of proteins, known as ASPPs (ankyrin-repeat-, SH3-domain- and proline-rich-region-containing proteins), has led to the discovery of a novel mechanism that selectively regulates the apoptotic function, but not the cell-cycle-arrest function, of p53, and gives an insight into how p53 responds to different stress signals. ASPPs might be new molecular targets for cancer therapy.

摘要翻译： 

人类癌症中最常突变的基因之一——肿瘤抑制基因p53（TP53）——能够诱导细胞周期停滞和凋亡。p53的凋亡功能与其抑癌作用紧密相关，且许多癌症疗法的疗效依赖于这一功能。新发现的蛋白家族ASPPs（含锚蛋白重复序列、SH3结构域及富含脯氨酸区的蛋白质）揭示了一种选择性调控p53凋亡功能而非细胞周期 arrest 功能的新机制，并阐明了p53如何应对不同应激信号。ASPPs可能成为癌症治疗的新分子靶点。

原文链接：

ASPPs and cancer