Intracellular localization of the tumor suppressor HtrA1/Prss11 and its association with HPV16 E6 and E7 proteins

Intracellular localization of the tumor suppressor HtrA1/Prss11 and its association with HPV16 E6 and E7 proteins
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DOI:
10.1002/jcb.21804
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发表时间:
2008-09-01
影响因子:
4
通讯作者:
Pan, Weihua
Pan, Weihua
中科院分区:
生物学2区
文献类型:
--
作者:
Clawson, Gary A.;Bui, Vuong;Pan, Weihua

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我们对一种似乎与致癌作用有关的核蛋白酶有着长期的兴趣。我们最近确定的蛋白酶高温需求因子A1(HtrA 1),也被称为Prss 11,这是一个氧化应激反应蛋白酶家族的成员。HtrA 1被归类为一种参与TGF β信号传导的分泌型蛋白酶,但最近的研究表明HtrA 1是一种肿瘤抑制因子。在这里,我们表明:在细胞内和核内发现了HtrA 1的加工形式,并且HtrA 1的活性核内形式显示出与Mr 29,000相似。此外,HPV E6/E7蛋白的表达与HtrA 1(最显著的是核形式)的转录后上调相关,并且发现HtrA 1与HPV E6和E7蛋白都相关。
We have a long-standing interest in a nuclear protease which appears to be involved in carcinogenesis. We recently identified the protease as high temperature requirement factor A 1 (HtrA1), also known as Prss11, which is member of an oxidative stress-response family of proteases. HtrA1 has been classified as a secreted protease involved in TGF beta signaling, but recent work has shown HtrA1 to be a tumor suppressor. Here we show that: processed forms of HtrA1 are found intracellularly and intranuclearly, and the active intranuclear form of HtrA1 shows an similar to Mr 29,000. Further, expression of HPV E6/E7 proteins is associated with a post-transcriptional up-regulation of HtrA1 (most notably the nuclear form), and HtrA1 is found associated with both HPV E6 and E7 proteins.