Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57(KIP2), on chromosome 11p15
Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57(KIP2), on chromosome 11p15
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DOI：
10.1073/pnas.93.7.3026
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发表时间：
1996-04-02
影响因子：
11.1
通讯作者：
Feinberg, AP
中科院分区：
文献类型：
--
作者：
Matsuoka, S;Thompson, JS;Feinberg, AP
人类癌症中染色体 11p15 的亲本起源特异性改变表明涉及一种或多种母体表达的印记基因，这些基因参与胚胎肿瘤抑制和癌症易感性 Beckwith-Wiedemann 综合征 (BWS)。编码细胞周期蛋白依赖性激酶抑制剂 p57(KIP2) 的基因，其过度表达导致 G(1) 期阻滞，最近被克隆并定位到该条带。我们发现 p57(KIP2) 基因是印记的，与母体等位基因的优先表达，然而，印记不是绝对的，因为父体等位基因在大多数组织中也以低水平表达，并且其水平与胎儿脑和一些胚胎肿瘤中母体等位基因相当，p57(KIP2)基因的生化功能、染色体位置和印记与11p15.5处肿瘤抑制基因的预测特性相匹配，然而，由于p57(KIP2)基因为500 kb 着丝粒到编码胰岛素样生长因子 2 的基因，它可能是包含其他印记基因的大结构域的一部分，因此，杂合性的丧失或印记的丧失可能同时影响该位点的多个基因，这些基因共同促成在 BWS 和胚胎肿瘤中被破坏的肿瘤和/或生长抑制功能。
Parental origin-specific alterations of chromosome 11p15 in human cancer suggest the involvement of one or more maternally expressed Imprinted genes involved in embryonal tumor suppression and the cancer-predisposing Beckwith-Wiedemann syndrome (BWS), The gene encoding cyclin-dependent kinase inhibitor p57(KIP2), whose overexpression causes G(1) phase arrest, was recently cloned and mapped to this band, We find that the p57(KIP2) gene is imprinted, with preferential expression of the maternal allele, However, the Imprint is not absolute, as the paternal allele is also expressed at low levels in most tissues, and at levels comparable to the maternal allele in fetal brain and some embryonal tumors, The biochemical function, chromosomal location, and imprinting of the p57(KIP2) gene match the properties predicted for a tumor suppressor gene at 11p15.5, However, as the p57(KIP2) gene is 500 kb centromeric to the gene encoding insulin-like growth factor 2, it is likely to be part of a large domain containing other imprinted genes, Thus, loss of heterozygosity or loss of imprinting might simultaneously affect several genes at this locus that together contribute to tumor and/or growth-suppressing functions that are disrupted in BWS and embryonal tumors.