Rolén Ulrika, Kobzeva Vera, Gasparjan Natalja, Ovaa Huib, Winberg Gösta, Kisseljov Fjodor, Masucci Maria G
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Mol Carcinog. 2006 Apr;45(4):260-9. doi: 10.1002/mc.20177.
Ubiquitin specific proteases (USPs) regulate the production and recycling of ubiquitin and are thereby critically involved in the control of cell growth, differentiation, and apoptosis. Increasing evidence implicates deregulation of USPs in malignant transformation but there is very little information on the overall and specific activity of USPs in normal and tumor tissues. We have used a chemistry-based functional proteomics approach to profile the activities of individual USPs in biopsies of human papillomavirus (HPV) carrying cervical carcinoma and adjacent normal tissue. To assess the contribution of HPV proteins, USP activity was also compared in HPV positive and negative cervical carcinoma cell lines and HPV E6/E7 immortalized human keratinocytes. The activity of the C-terminal hydrolases UCH-L3 and UCH37 was upregulated in the majority of tumor tissues compared to the adjacent normal tissues. UCH-L1 activity was lower in a significant proportion of the tumors but to a less extent in advanced tumors. In accordance with the relatively low UCH-L1 activity in tumor biopsies, UCH-L1 was detected only in one out of eight cervical carcinoma lines. UCH-L1, UCH-L3, USP7, and USP9X activity was upregulated following HPV E6/E7 immortalization of keratinocytes, suggesting a role of these enzymes in growth transformation.
泛素特异性蛋白酶（USPs）调节泛素的产生和循环利用，因此在细胞生长、分化和凋亡的控制中起着关键作用。越来越多的证据表明，USPs失调与恶性转化有关，但关于USPs在正常组织和肿瘤组织中的整体及特定活性的信息却非常少。我们采用了基于化学的功能蛋白质组学方法，对携带人乳头瘤病毒（HPV）的宫颈癌活检组织及相邻正常组织中各个USPs的活性进行了分析。为了评估HPV蛋白的作用，我们还比较了HPV阳性和阴性宫颈癌细胞系以及HPV E6/E7永生化人角质形成细胞中USP的活性。与相邻正常组织相比，大多数肿瘤组织中C末端水解酶UCH-L3和UCH37的活性上调。在相当一部分肿瘤中，UCH-L1活性较低，但在晚期肿瘤中程度较轻。鉴于肿瘤活检组织中UCH-L1活性相对较低，在8个宫颈癌细胞系中只有1个检测到UCH-L1。角质形成细胞经HPV E6/E7永生化后，UCH-L1、UCH-L3、USP7和USP9X的活性上调，表明这些酶在生长转化中发挥作用。
