文章：

LKB1——小肠及其他部位的主要肿瘤抑制因子

LKB1 — A master tumour suppressor of the small intestine and beyond

原文发布日期：2002-07-01

DOI: 10.1038/nrc843

类型: Review Article

开放获取: 否

要点：

1. Peutz–Jeghers syndrome (PJS) is an autosomal polyposis disorder that is characterized by cancer predisposition at a young age. It is associated with inactivating mutations in the LKB1 gene.
2. Different hamartomatous polyposis syndromes are associated with different types of genetic defects. PJS is characterized by gastrointestinal hamartomas that have a smooth-muscle core.
3. LKB1 is required for normal fetal development and is present in apoptotic intestinal cells. LKB1 has been shown to be involved in p53-mediated apoptosis. LKB1 phosphorylates p53 at low levels, which might be required for p53 activation.
4. LKB1 has also been shown to control cell proliferation. It interacts with the chromatin remodelling protein brahma-related gene-1 (BRG1), and also with the cell-cycle regulatory proteins LKB1-interacting protein 1 (LIP1) and WAF1.
5. LKB1 is therefore an important tumour suppressor that might be developed as a cancer therapeutic target.

要点翻译：

1. Peutz-Jeghers综合征（PJS）是一种常染色体显性遗传性息肉病，其特征为青少年时期易发癌症。该疾病与LKB1基因的失活突变相关。
2. 不同类型的错构瘤性息肉病综合征与不同遗传缺陷相关。PJS以胃肠道错构瘤为特征，此类息肉具有平滑肌核心。
3. LKB1基因是胎儿正常发育所必需的，且存在于凋亡的肠道细胞中。研究证实LKB1参与p53介导的细胞凋亡过程，它能以低水平磷酸化p53，这可能是p53激活的必要条件。
4. LKB1还被证明具有调控细胞增殖的功能。该基因与染色质重塑蛋白BRG1（brahma相关基因-1）、细胞周期调控蛋白LKB1互作蛋白1（LIP1）以及WAF1蛋白相互作用。
5. 因此，LKB1是重要的肿瘤抑制因子，有望成为癌症治疗的靶点。

英文摘要：

Peutz–Jeghers syndrome (PJS) is a rare, inherited intestinal polyposis syndrome that is associated with a significantly increased risk of several types of cancer — particularly those of the gastrointestinal and reproductive systems. Most cases of PJS have been associated with loss-of-function mutations in the ubiquitously expressed LKB1 gene, which encodes a serine/ threonine kinase. Recent studies have begun to illustrate the molecular mechanisms by which LKB1 functions as an important new tumour suppressor.

摘要翻译： 

Peutz–Jeghers 综合征（PJS）是一种罕见的遗传性肠道息肉病综合征，与多种癌症（尤其是胃肠道和生殖系统癌症）的显著增加风险相关。大多数PJS病例与普遍表达的LKB1基因的功能丧失突变有关，该基因编码一种丝氨酸/苏氨酸激酶。近期研究开始阐明LKB1作为一种重要的新型肿瘤抑制因子的分子机制。

原文链接：

LKB1 — A master tumour suppressor of the small intestine and beyond