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000128312 1001_ $$aBoege, Yannick$$b0
000128312 245__ $$aA Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development.
000128312 260__ $$aCambridge, Mass.$$bCell Press$$c2017
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000128312 520__ $$aConcomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX.
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000128312 650_7 $$2NLM Chemicals$$aFadd protein, mouse
000128312 650_7 $$2NLM Chemicals$$aFas-Associated Death Domain Protein
000128312 650_7 $$2NLM Chemicals$$aHistones
000128312 650_7 $$2NLM Chemicals$$aMcl1 protein, mouse
000128312 650_7 $$2NLM Chemicals$$aMyeloid Cell Leukemia Sequence 1 Protein
000128312 650_7 $$2NLM Chemicals$$aReceptors, Tumor Necrosis Factor, Type I
000128312 650_7 $$2NLM Chemicals$$agamma-H2AX protein, mouse
000128312 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aReceptor-Interacting Protein Serine-Threonine Kinases
000128312 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aRipk1 protein, mouse
000128312 650_7 $$0EC 2.7.11.24$$2NLM Chemicals$$aJNK Mitogen-Activated Protein Kinases
000128312 650_7 $$0EC 3.4.22.-$$2NLM Chemicals$$aCaspase 8
000128312 7001_ $$aMalehmir, Mohsen$$b1
000128312 7001_ $$aHealy, Marc E$$b2
000128312 7001_ $$aBettermann, Kira$$b3
000128312 7001_ $$aLorentzen, Anna$$b4
000128312 7001_ $$aVucur, Mihael$$b5
000128312 7001_ $$aAhuja, Akshay K$$b6
000128312 7001_ $$aBöhm, Friederike$$b7
000128312 7001_ $$aMertens, Joachim C$$b8
000128312 7001_ $$aShimizu, Yutaka$$b9
000128312 7001_ $$aFrick, Lukas$$b10
000128312 7001_ $$aRemouchamps, Caroline$$b11
000128312 7001_ $$aMutreja, Karun$$b12
000128312 7001_ $$aKähne, Thilo$$b13
000128312 7001_ $$aSundaravinayagam, Devakumar$$b14
000128312 7001_ $$aWolf, Monika J$$b15
000128312 7001_ $$aRehrauer, Hubert$$b16
000128312 7001_ $$aKoppe, Christiane$$b17
000128312 7001_ $$aSpeicher, Tobias$$b18
000128312 7001_ $$aPadrissa-Altés, Susagna$$b19
000128312 7001_ $$aMaire, Renaud$$b20
000128312 7001_ $$aSchattenberg, Jörn M$$b21
000128312 7001_ $$aJeong, Ju-Seong$$b22
000128312 7001_ $$aLiu, Lei$$b23
000128312 7001_ $$0P:(DE-HGF)0$$aZwirner, Stefan$$b24
000128312 7001_ $$aBoger, Regina$$b25
000128312 7001_ $$aHüser, Norbert$$b26
000128312 7001_ $$aDavis, Roger J$$b27
000128312 7001_ $$aMüllhaupt, Beat$$b28
000128312 7001_ $$aMoch, Holger$$b29
000128312 7001_ $$aSchulze-Bergkamen, Henning$$b30
000128312 7001_ $$aClavien, Pierre-Alain$$b31
000128312 7001_ $$aWerner, Sabine$$b32
000128312 7001_ $$aBorsig, Lubor$$b33
000128312 7001_ $$aLuther, Sanjiv A$$b34
000128312 7001_ $$aJost, Philipp J$$b35
000128312 7001_ $$aWeinlich, Ricardo$$b36
000128312 7001_ $$aUnger, Kristian$$b37
000128312 7001_ $$aBehrens, Axel$$b38
000128312 7001_ $$aHillert, Laura$$b39
000128312 7001_ $$aDillon, Christopher$$b40
000128312 7001_ $$aDi Virgilio, Michela$$b41
000128312 7001_ $$aWallach, David$$b42
000128312 7001_ $$aDejardin, Emmanuel$$b43
000128312 7001_ $$0P:(DE-He78)1ba2900406378e069d32db376c7818db$$aZender, Lars$$b44$$udkfz
000128312 7001_ $$aNaumann, Michael$$b45
000128312 7001_ $$aWalczak, Henning$$b46
000128312 7001_ $$aGreen, Douglas R$$b47
000128312 7001_ $$aLopes, Massimo$$b48
000128312 7001_ $$aLavrik, Inna$$b49
000128312 7001_ $$aLuedde, Tom$$b50
000128312 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwalder, Mathias$$b51$$udkfz
000128312 7001_ $$aWeber, Achim$$b52
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