Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Jost, PJ; Grabow, S; Gray, D; McKenzie, MD; Nachbur, U; Huang, DC; Bouillet, P; Thomas, HE; Borner, C; Silke, J; Strasser, A; Kaufmann, T.
XIAP discriminates between type I and type II FAS-induced apoptosis.
Nature. 2009; 460(7258):1035-1039 Doi: 10.1038/nature08229 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Führende Autor*innen der Med Uni Graz
Jost Philipp

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Apoptosis -
BH3 Interacting Domain Death Agonist Protein - deficiency
BH3 Interacting Domain Death Agonist Protein - genetics
Biomimetic Materials - pharmacology
Caspase Inhibitors -
Enzyme Activation -
Fas Ligand Protein - metabolism
Female -
Hepatitis - metabolism
Hepatitis - pathology
Hepatocytes - cytology
Hepatocytes - drug effects
Hepatocytes - metabolism
Male -
Mice -
Mice, Inbred C57BL -
Signal Transduction -
Thymus Gland - cytology
Thymus Gland - drug effects
X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors
X-Linked Inhibitor of Apoptosis Protein - deficiency
X-Linked Inhibitor of Apoptosis Protein - genetics
X-Linked Inhibitor of Apoptosis Protein - metabolism
fas Receptor - antagonists & inhibitors
fas Receptor - immunology
fas Receptor - metabolism

© Med Uni Graz Impressum