scholarly journals Smac/Diablo Antagonizes Ubiquitin Ligase Activity of Inhibitor of Apoptosis Proteins

2004 ◽  
Vol 279 (26) ◽  
pp. 26906-26914 ◽  
Author(s):  
Emma M. Creagh ◽  
Brona M. Murphy ◽  
Patrick J. Duriez ◽  
Colin S. Duckett ◽  
Seamus J. Martin
Keyword(s):  
Ubiquitin Ligase ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Proteins ◽  
Ubiquitin Ligase Activity ◽  
Apoptosis Proteins

Inhibitor of apoptosis proteins (IAP) in adrenocortical tumors

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
B Altieri ◽  
S Sbiera ◽  
S Della Casa ◽  
S Steinhauer ◽  
V Wild ◽  
...  
Keyword(s):  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Proteins ◽  
Adrenocortical Tumors ◽  
Apoptosis Proteins

scholarly journals Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus

2015 ◽  
Vol 112 (18) ◽  
pp. 5797-5802 ◽  
Author(s):  
Gregor Ebert ◽  
Simon Preston ◽  
Cody Allison ◽  
James Cooney ◽  
Jesse G. Toe ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Proteins ◽  
Immunocompetent Mouse ◽  
Immune Mediated ◽  
B Virus ◽  
Chronic Hbv ◽  
Apoptosis Proteins

Hepatitis B virus (HBV) infection can result in a spectrum of outcomes from immune-mediated control to disease progression, cirrhosis, and liver cancer. The host molecular pathways that influence and contribute to these outcomes need to be defined. Using an immunocompetent mouse model of chronic HBV infection, we identified some of the host cellular and molecular factors that impact on infection outcomes. Here, we show that cellular inhibitor of apoptosis proteins (cIAPs) attenuate TNF signaling during hepatitis B infection, and they restrict the death of infected hepatocytes, thus allowing viral persistence. Animals with a liver-specific cIAP1 and total cIAP2 deficiency efficiently control HBV infection compared with WT mice. This phenotype was partly recapitulated in mice that were deficient in cIAP2 alone. These results indicate that antagonizing the function of cIAPs may promote the clearance of HBV infection.

scholarly journals Antagonism of Inhibitor of Apoptosis Proteins Increases Bone Metastasis via Unexpected Osteoclast Activation

2012 ◽  
Vol 3 (2) ◽  
pp. 212-223 ◽  
Author(s):  
Chang Yang ◽  
Jennifer L. Davis ◽  
Rong Zeng ◽  
Paras Vora ◽  
Xinming Su ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Proteins ◽  
Osteoclast Activation ◽  
Apoptosis Proteins

scholarly journals The RING Domain of cIAP1 Mediates the Degradation of RING-bearing Inhibitor of Apoptosis Proteins by Distinct Pathways

2008 ◽  
Vol 19 (7) ◽  
pp. 2729-2740 ◽  
Author(s):  
Herman H. Cheung ◽  
Stéphanie Plenchette ◽  
Chris J. Kern ◽  
Douglas J. Mahoney ◽  
Robert G. Korneluk
Keyword(s):  
Fas Ligand ◽  
Ring Domain ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Proteins ◽  
Down Regulation ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Apoptosis Proteins

The Inhibitor of Apoptosis proteins (IAPs) are key repressors of apoptosis. Several IAP proteins contain a RING domain that functions as an E3 ubiquitin ligase involved in the ubiquitin-proteasome pathway. Here we investigated the interplay of ubiquitin-proteasome pathway and RING-mediated IAP turnover. We found that the CARD-RING domain of cIAP1 (cIAP1-CR) is capable of down-regulating protein levels of RING-bearing IAPs such as cIAP1, cIAP2, XIAP, and Livin, while sparing NAIP and Survivin, which do not possess a RING domain. To determine whether polyubiquitination was required, we tested the ability of cIAP1-CR to degrade IAPs under conditions that impair ubiquitination modifications. Remarkably, although the ablation of E1 ubiquitin-activating enzyme prevented cIAP1-CR–mediated down-regulation of cIAP1 and cIAP2, there was no impact on degradation of XIAP and Livin. XIAP mutants that were not ubiquitinated in vivo were readily down-regulated by cIAP1-CR. Moreover, XIAP degradation in response to cisplatin and doxorubicin was largely prevented in cIAP1-silenced cells, despite cIAP2 up-regulation. The knockdown of cIAP1 and cIAP2 partially blunted Fas ligand-mediated down-regulation of XIAP and protected cells from cell death. Together, these results show that the E3 ligase RING domain of cIAP1 targets RING-bearing IAPs for proteasomal degradation by ubiquitin-dependent and -independent pathways.

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