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鉴定和发育表达小鼠 Plu-1,它是人类核蛋白(PLU-1)的同源物,在乳腺癌中特异性上调。

Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer.

机构信息

Breast Cancer Biology Group, Cancer Research UK, Guy's Hospital, St Thomas Street, London SE1 9RT, UK.

出版信息

Mech Dev. 2002 Dec;119 Suppl 1:S239-46. doi: 10.1016/s0925-4773(03)00123-0.

Abstract

PLU-1 is a novel breast cancer associated nuclear protein containing highly conserved domains including the PLU domain, putative DNA/chromatin binding motifs, and PHD/LAP domains. Here we report the cloning of the mouse homologue (Plu-1), and document its expression in adult tissues, mammary tumours and the embryo. The overall homology with human PLU-1 is 94% at the protein level, with almost 100% identity in the conserved domains, suggesting functional conservation. As with human PLU-1 the expression of Plu-1 in adult tissues is restricted, with high expression being seen only in testis, while expression in mammary tumours from c-neu transgenic mice is high. Plu-1 is also differentially expressed in the adult mammary gland. In the developing embryo Plu-1 is expressed in a temporally restricted fashion with tissue specific expression being limited to parts of the developing brain, whisker follicle, mammary bud, thymus, limbs, intervertebral disc, olfactory epithelium, teeth, eye, and stomach. The temporal and spatial expression patterns of the transcription factors Bf-1 and Pax9, recently found to bind to PLU-1 through the PLU domain overlap with Plu-1 expression during development. Thus Plu-1 appears to play an important role in mouse embryonic development which may involve interaction with Pax9 and Bf-1.

摘要

PLU-1 是一种新型的乳腺癌相关核蛋白,含有高度保守的结构域,包括 PLU 结构域、假定的 DNA/染色质结合基序以及 PHD/LAP 结构域。在这里,我们报告了小鼠同源物(Plu-1)的克隆,并记录了其在成年组织、乳腺肿瘤和胚胎中的表达。与人类 PLU-1 的整体同源性在蛋白质水平上为 94%,在保守结构域中几乎达到 100%的同一性,表明功能的保守性。与人类 PLU-1 一样,Plu-1 在成年组织中的表达受到限制,仅在睾丸中高表达,而在 c-neu 转基因小鼠的乳腺肿瘤中表达较高。Plu-1 在成年乳腺中也有差异表达。在胚胎发育过程中,Plu-1 以时间限制的方式表达,组织特异性表达仅限于大脑、胡须滤泡、乳腺芽、胸腺、四肢、椎间盘、嗅上皮、牙齿、眼睛和胃的部分发育区域。最近发现通过 PLU 结构域与 PLU-1 结合的转录因子 Bf-1 和 Pax9 的时空表达模式与 Plu-1 的表达重叠。因此,Plu-1 似乎在小鼠胚胎发育中发挥着重要作用,这可能涉及与 Pax9 和 Bf-1 的相互作用。

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