Lamina-associated polypeptide (LAP)2α and other LEM proteins in cancer biology.
Lamina-associated polypeptide (LAP)2α and other LEM proteins in cancer biology.
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DOI：
10.1007/978-1-4899-8032-8_7
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发表时间：
2014
影响因子：
--
通讯作者：
Foisner, Roland
中科院分区：
文献类型：
--
作者：
Brachner, Andreas;Foisner, Roland
关键词：
LEM 蛋白由染色质相关蛋白的异质家族组成，它们共享 LEM 结构域，这是介导与 DNA 相关蛋白、自动整合屏障因子 (BAF) 相互作用的结构基序。大多数 LEM 蛋白是内核膜的整合蛋白，并与核纤层相关，核纤层是核周边核纤层中间丝蛋白的结构支架，参与核机械功能和（异）染色质组织。一些 LEM 蛋白，例如层相关多肽 (LAP)2α 和锚蛋白以及含有 LEM 结构域的蛋白 (Ankle)1 缺乏跨膜结构域，并且分别定位于整个核质和细胞质。据报道，LAP2α 通过影响组织祖细胞中视网膜母细胞瘤蛋白的活性来调节细胞增殖，并且大量研究表明 LAP2α 在癌症中上调。 Ankle1 是一种可能参与 DNA 损伤修复途径的核酸酶，Ankle1 基因中的单核苷酸多态性与乳腺癌和卵巢癌风险增加有关。在本章中，我们描述了 LEM 蛋白（特别是 LAP2α 和 Ankle1）参与肿瘤发生的潜在机制，并提供了 LAP2α 表达可能是肿瘤分析的有价值的诊断和预后标志物的证据。
The LEM proteins comprise a heterogeneous family of chromatin-associated proteins that share the LEM domain, a structural motif mediating interaction with the DNA associated protein, Barrier-to-Autointegration Factor (BAF). Most of the LEM proteins are integral proteins of the inner nuclear membrane and associate with the nuclear lamina, a structural scaffold of lamin intermediate filament proteins at the nuclear periphery, which is involved in nuclear mechanical functions and (hetero-)chromatin organization. A few LEM proteins, such as Lamina-associated polypeptide (LAP)2α and Ankyrin and LEM domain-containing protein (Ankle)1 lack transmembrane domains and localize throughout the nucleoplasm and cytoplasm, respectively. LAP2α has been reported to regulate cell proliferation by affecting the activity of retinoblastoma protein in tissue progenitor cells and numerous studies showed upregulation of LAP2α in cancer. Ankle1 is a nuclease likely involved in DNA damage repair pathways and single nucleotide polymorphisms in the Ankle1 gene have been linked to increased breast and ovarian cancer risk. In this chapter we describe potential mechanisms of the involvement of LEM proteins, particularly of LAP2α and Ankle1 in tumorigenesis and we provide evidence that LAP2α expression may be a valuable diagnostic and prognostic marker for tumor analyses.
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