The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis
The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis
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DOI：
10.1038/sj.onc.1209353
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发表时间：
2006-06-01
期刊：
影响因子：
8
通讯作者：
Batra, S. K.
中科院分区：
文献类型：
--
作者：
Moniaux, N.;Nemos, C.;Batra, S. K.
在胰腺癌细胞中的19 q13扩增子包含一个新的胰腺分化2（PD 2）基因（登录号AJ 401156），这是通过差异筛选分析确定的。PD 2是RNA聚合酶II相关因子1（hPaf 1）的人类同源物。在酵母中，Paf 1是转录机制的一部分，作为复合物Rad 6-Bre 1、COMPASS-Dot 1 p和RNA聚合酶II的磷酸化羧基末端结构域之间的对接蛋白。因此，Paf 1通过组蛋白H2 B泛素化和组蛋白H3甲基化直接参与转录延伸。PD 2序列从果蝇到人类高度保守，啮齿动物和人类之间的同源性高达98%，表明PD 2/hPaf 1在维持细胞稳态方面的功能重要性。PD 2是由RNA识别基序、DEAD盒、天冬氨酸/丝氨酸（DS）结构域、染色体凝聚调节结构域和myc型螺旋-环-螺旋结构域组成的模块蛋白。我们的研究结果进一步表明，PD 2是一个核80 kDa的蛋白，它与RNA聚合酶II相互作用。此外，我们已经证明，PD 2在NIH 3 T3细胞中的过表达导致体外生长速率和体内肿瘤形成的增强。总之，本文提供了强有力的证据表明，PD 2/hPaf 1的过表达参与癌症的发展。
The 19q13 amplicon in pancreatic cancer cells contains a novel pancreatic differentiation 2 (PD2) gene (accession number AJ401156), which was identified by differential screening analysis. PD2 is the human homologue of the RNA polymerase II-associated factor 1 (hPaf1). In yeast, Paf1 is part of the transcription machinery, acting as a docking protein in between the complexes Rad6-Bre1, COMPASS-Dot1p, and the phosphorylated carboxyl terminal domain of the RNA polymerase II. As such, Paf1 is directly involved in transcription elongation via histone H2B ubiquitination and histone H3 methylation. The PD2 sequence is highly conserved from Drosophila to humans with up to 98% identity between rodent and human, suggesting the functional importance of PD2/hPaf1 to maintain cellular homeostasis. PD2 is a modular protein composed of RNA recognition motif, DEAD-boxes, an aspartic/serine (DS)-domain, a regulator of the chromosome condensation domain and myc-type helix-loop-helix domains. Our results further showed that PD2 is a nuclear 80kDa protein, which interacts with RNA polymerase II. In addition, we have demonstrated that the overexpression of PD2 in the NIH 3T3 cells result in enhanced growth rates in vitro and tumor formation in vivo. Altogether, this paper presents strong evidence that the overexpression of PD2/hPaf1 is involved in cancer development.