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000128242 0247_ $$2doi$$a10.1007/s00403-017-1757-9
000128242 0247_ $$2pmid$$apmid:28647894
000128242 0247_ $$2ISSN$$a0340-3696
000128242 0247_ $$2ISSN$$a1432-069X
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000128242 037__ $$aDKFZ-2017-04259
000128242 041__ $$aeng
000128242 082__ $$a610
000128242 1001_ $$aZupancic, Tina$$b0
000128242 245__ $$aKeratin gene mutations influence the keratinocyte response to DNA damage and cytokine induced apoptosis.
000128242 260__ $$aBerlin$$bSpringer$$c2017
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000128242 520__ $$aThe keratin filament cytoskeleton is vital to the normal function of epithelial cells. It provides structural support and regulates different aspects of cell metabolism. Mutations in keratins 5 and 14 cause a skin fragility disorder, epidermolysis bullosa simplex (EBS). Patients with severe EBS have an increased cumulative risk for basal cell carcinoma. In this study, we tested how keratin 5 and 14 mutant EBS patient-derived keratinocytes behave in the face of two different types of stressors that are able to induce cell death: ionizing radiation and cytokines TNF-α and TRAIL. The data point out to a substantial difference between how normal and keratin mutant keratinocytes deal with such stresses. When case of DNA damage, the ATM/Chk2-pathway is one of the two main tracks that can prevent the progression of mitosis and so allow repair. This was altered in all investigated keratin mutants with a particular down-regulation of the activated form of checkpoint kinase 2 (pChk2). Keratin mutants also appear less sensitive than normal cells to treatment with TNF-α or TRAIL, and this may be linked to the up-regulation of two pro-survival proteins, Bcl-2 and FLIP. Such changes are likely to have a profound effect on mutant keratinocytes ability to survive and withstand stress, and in theory this may be also a contributing factor to cell transformation.
000128242 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0
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000128242 7001_ $$aSersa, Gregor$$b1
000128242 7001_ $$aTörmä, Hans$$b2
000128242 7001_ $$aLane, Ellen Birgitte$$b3
000128242 7001_ $$0P:(DE-He78)7892a89fee19b8e3912c7423d660765d$$aHerrmann, Harald$$b4$$udkfz
000128242 7001_ $$aKomel, Radovan$$b5
000128242 7001_ $$00000-0001-8045-7868$$aLiovic, Mirjana$$b6
000128242 773__ $$0PERI:(DE-600)1458448-7$$a10.1007/s00403-017-1757-9$$gVol. 309, no. 7, p. 587 - 593$$n7$$p587 - 593$$tArchives of dermatological research$$v309$$x1432-069X$$y2017
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000128242 9141_ $$y2017
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