X-linked inhibitor of apoptosis

Tun C, Guo W, Nguyen H, Yun B, Libby RT, Morrison RS, Garden GA (2007) Activation of the extrinsic caspase pathway in cultured cortical neurons requires p53-mediated down-regulation of the X-linked inhibitor of apoptosis protein to induce apoptosis. J Neurochem 102 1206-1219... 

Holcik, M., and Korneluk, R. G. (2000). Functional characterization of the X-linked inhibitor of apoptosis (XIAP) internal ribosome entry site element Role of La autoantigen in XIAP translation. Mol. Cell Biol. 20, 4648-4657. 

Suzuki, Y., Y. Nakabayashi, and R. Takahashi, Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes protea-... 

This kind of interaction can be considered as the most challenging among our application examples because it is intrinsically characterized by the lowest degree of information [14]. We demonstrate the application of the GBPM procedure to a member of a family of proteins involved in the regulation of apoptosis, the X-linked inhibitor of apoptosis (XIAP). Its third baculovirus IAP repeat domain (BIR3) recognizes compounds 1-5 as shown in Fig. 7.2. 

Cheung, H. H., LaCasse, E. C., Korneluk, R. G. (2006) X-linked inhibitor of apoptosis antagonism strategies in cancer treatment. Clinical Cancer Research, 12, 3238-3242. 

Perrelet D, Perrin FE, Liston P, Korneluk RG, MacKenzie A, Ferrer-Alcon M, Kato AC (2004) Motoneuron resistance to apoptotic cell death in vivo correlates with the ratio between X-linked inhibitor of apoptosis proteins (XIAPs) and its inhibitor, XlAP-assodated factor 1. J Neurosci 24 3777-3785... 

Proteins containing these domains have been shown to inhibit caspases. At least 8 members of the mammahan family of lAP proteins containing two to three copies of the BIR domain have been identified. These BIR domains may function differently in the inhibition of the caspases. The third BIR repeat, BIR3, of the X-linked protein, X-linked inhibitor of apoptosis protein (XIAP) binds to monomeric initiator caspase-9 to form a heterodimer and thus prevents caspase-9 from forming its functional dimer, resulting in loss of enzymatic activity. ... 

Huang Y, et al. Requirement of both the second and third BIR domains for the relief of X-linked inhibitor of apoptosis protein 120. (XIAP)-mediated caspase inhibition by Smac. J. Biol. Chem. 2003 278 49517-49522. 

Splan KE, Allen IE, McLendon GL. Biochemical basis for enhanced binding of Peptide dimers to x-linked inhibitor of apoptosis protein. Biochemistry 2007 46 11938-11944. 

Figure 1 shows the crystal structure of X-linked inhibitor of apoptosis (XIAP) binding with small-molecule inhibitor, which helps to restore apoptosis and offset the cancerous state. The availability of many protein structures has enabled researchers... 

TER TMEV TMT TN toll-like receptor Theiler s mouse encephalomyelids virus dime thy Idn terminal nuclei X-ALD XIAP X-adrenoleukody s dophy X-linked inhibitor of apoptosis protein... 

Leaman DW, Chawla-Sarkar M,Vyas K, Reheman M,Tamai K,Toji S, and Borden EC. Identification of X-linked Inhibitor of Apoptosis-associated Eactor-1 as an Interferon-stimulated Gene That Augments TRAIL Apo2L-induced Apoptosis. J Biol Chem 277 28504-28511,2002. 

X-linked inhibitor of apoptosis (XIAP) is a monoclonal antibody shown to be a useful marker for distinguishing malignant from benign groups of cells. XIAP is also demonstrated in a variety of adenocarcinomas (up to 54%). However, weak and focal staining is seen in mesothelial cells (up to 11%). 

Sun H, Stuckey JA, Nikolovska-Coleska Z et al (2008) Structure-based design, synthesis, evaluation and crystallographic studies of conformationally constrained Smac mimetics as inhibitors of the X-linked inhibitor of apoptosis protein (XIAP). J Med Chem 51 7169-7180... 

Nikolovska-Coleska Z, Meagher JL, Jiang S et al (2008) Interaction of a cyclic, bivalent Smac mimetic with the X-linked inhibitor of apoptosis protein. Biochemistry 47 9811-9824... 

Suzuki Y, Nakabayashi Y, Nakata K et al (2001) X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes. J Biol Chem 276(29) 27058-27063... 

Sasaki H, Sheng Y, Kotsuji F et al (2000) Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells. Cancer Res 60(20) 5659-5666... 

Cummings, J., Ward, T.H., LaCasse, E., Lefebvre, C., St Jean, M., Durkin, J., Ranson, M., and Dive, C. (2005) Validation of pharmacodynamic assays to evaluate the clinical efficacy of an antisense compound (AEG 35156) targeted to the X linked inhibitor of apoptosis protein XIAP. British Journal of Cancer, 92, 532 538. 

Yamagiwa, Y., Marienfeld, C., Meng, F., Holcik, M., and Patel, T. Translational regulation of x-linked inhibitor of apoptosis protein by interleukin-6 A novel mechanism of tumor cell survival. Cancer Res 64, 1293-1298 (2004). 

Holcik M, Yeh C, Korneluk RG et al. Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death. Oncogene 2000 ... 

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