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

2007 ◽  
Vol 102 (4) ◽  
pp. 1206-1219 ◽  
Author(s):  
Christina Tun ◽  
Weiqun Guo ◽  
Huy Nguyen ◽  
Bomy Yun ◽  
Randell T. Libby ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Inhibitor Of Apoptosis ◽  
Down Regulation ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Caspase Pathway ◽  
Cultured Cortical Neurons

scholarly journals E-Cadherin Is Required for Caveolin-1-Mediated Down-Regulation of the Inhibitor of Apoptosis Protein Survivin via Reduced β-Catenin-Tcf/Lef-Dependent Transcription

2007 ◽  
Vol 27 (21) ◽  
pp. 7703-7717 ◽  
Author(s):  
Vicente A. Torres ◽  
Julio C. Tapia ◽  
Diego A. Rodriguez ◽  
Alvaro Lladser ◽  
Cristian Arredondo ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Molecular Mechanisms ◽  
Cell Model ◽  
Survivin Expression ◽  
Inhibitor Of Apoptosis ◽  
Down Regulation ◽  
Inhibitor Of Apoptosis Protein ◽  
Caveolin 1 ◽  
Apoptosis Protein ◽  
E Cadherin

ABSTRACT Caveolin-1 reportedly acts as a tumor suppressor and promotes events associated with tumor progression, including metastasis. The molecular mechanisms underlying such radical differences in function are not understood. Recently, we showed that caveolin-1 inhibits expression of the inhibitor of apoptosis protein survivin via a transcriptional mechanism involving the β-catenin-Tcf/Lef pathway. Surprisingly, while caveolin-1 expression decreased survivin mRNA and protein levels in HT29(ATCC) human colon cancer cells, this was not the case in metastatic HT29(US) cells. Survivin down-regulation was paralleled by coimmunoprecipitation and colocalization of caveolin-1 with β-catenin in HT29(ATCC) but not HT29(US) cells. Unlike HT29(ATCC) cells, HT29(US) cells expressed small amounts of E-cadherin that accumulated in intracellular patches rather than at the cell surface. Re-expression of E-cadherin in HT29(US) cells restored the ability of caveolin-1 to down-regulate β-catenin-Tcf/Lef-dependent transcription and survivin expression, as seen in HT29(ATCC) cells. In addition, coimmunoprecipitation and colocalization between caveolin-1 and β-catenin increased upon E-cadherin expression in HT29(US) cells. In human embryonic kidney HEK293T and HT29(US) cells, caveolin-1 and E-cadherin cooperated in suppressing β-catenin-Tcf/Lef-dependent transcription as well as survivin expression. Finally, mouse melanoma B16-F10 cells, another metastatic cell model with low endogenous caveolin-1 and E-cadherin levels, were characterized. In these cells, caveolin-1-mediated down-regulation of survivin in the presence of E-cadherin coincided with increased apoptosis. Thus, the absence of E-cadherin severely compromises the ability of caveolin-1 to develop activities potentially relevant to its role as a tumor suppressor.

Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer

2009 ◽  
Vol 8 (9) ◽  
pp. 2762-2770 ◽  
Author(s):  
Yun Dai ◽  
Liang Qiao ◽  
Kwok Wah Chan ◽  
Mo Yang ◽  
Jieyu Ye ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Inhibitor Of Apoptosis ◽  
Down Regulation ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

scholarly journals 15-Deoxy-Δ12,14-prostaglandin J2 induces apoptosis in human malignant B cells: an effect associated with inhibition of NF-κB activity and down-regulation of antiapoptotic proteins

Blood ◽  
2005 ◽  
Vol 105 (4) ◽  
pp. 1750-1758 ◽  
Author(s):  
Roberto Piva ◽  
Patrizia Gianferretti ◽  
Alessandra Ciucci ◽  
Riccardo Taulli ◽  
Giuseppe Belardo ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Inhibitor Of Apoptosis ◽  
B Cell Malignancies ◽  
Down Regulation ◽  
Inhibitor Of Apoptosis Protein ◽  
Ppar Γ ◽  
Apoptosis Protein ◽  
Induced Apoptosis ◽  
Constitutively Active

AbstractCyclopentenone prostaglandins are potent inhibitors of nuclear factor-κB (NF-κB), a transcription factor with a critical role in promoting inflammation and connected with multiple aspects of oncogenesis and cancer cell survival. In the present report, we investigated the role of NF-κB in the antineoplastic activity of the cyclopentenone prostaglandin 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) in multiple myeloma (MM) and Burkitt lymphoma (BL) cells expressing constitutively active NF-κB. 15d-PGJ2 was found to suppress constitutive NF-κB activity and potently induce apoptosis in both types of B-cell malignancies. 15d-PGJ2-induced apoptosis occurs through multiple caspase activation pathways involving caspase-8 and caspase-9, and is prevented by pretreatment with the pan-caspase inhibitor ZVAD (z-Val-Ala-Asp). NF-κB inhibition is accompanied by rapid down-regulation of NF-κB-dependent antiapoptotic gene products, including cellular inhibitor-of-apoptosis protein 1 (cIAP-1), cIAP-2, X-chromosome-linked inhibitor-of-apoptosis protein (XIAP), and FLICE-inhibitory protein (cFLIP). These effects were mimicked by the proteasome inhibitor MG-132, but not by the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist troglitazone, suggesting that 15d-PGJ2-induced apoptosis is independent of PPAR-γ. Knockdown of the NF-κB p65-subunit by lentiviral-mediated shRNA interference also resulted in apoptosis induction in malignant B cells with constitutively active NF-κB. The results indicate that inhibition of NF-κB plays a major role in the proapoptotic activity of 15d-PGJ2 in aggressive B-cell malignancies characterized by aberrant regulation of NF-κB. (Blood. 2005;105:1750-1758)

Turner syndrome patients with bicuspid aortic valves and renal malformations exhibit abnormal expression of X-linked inhibitor of apoptosis protein (XIAP)

2015 ◽  
Vol 28 (11-12) ◽  
Author(s):  
Ganesh S. Jevalikar ◽  
Margaret Zacharin ◽  
Mary White ◽  
Steven W. Yau ◽  
Winnie Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Turner Syndrome ◽  
Quantitative Polymerase Chain Reaction ◽  
Inhibitor Of Apoptosis ◽  
Aortic Valves ◽  
Inhibitor Of Apoptosis Protein ◽  
Abnormal Expression ◽  
Apoptosis Protein ◽  
Renal Malformations ◽  
Bicuspid Aortic Valves

AbstractWe analyzed mRNA expression of X-linked inhibitor of apoptosis protein (XIAP) in patients with Turner syndrome (TS) and examined its association with phenotypic features.XIAP mRNA expression levels were investigated in 98 patients with TS in total RNA extracted from blood leucocytes by real time quantitative polymerase chain reaction.Levels of XIAP mRNA were significantly lower in patients with bicuspid aortic valves (BAV; n=13) than those without (log XIAP –1.17±0.3 vs. –0.94±0.2, p=0.002). Significantly higher expression of XIAP mRNA was seen in patients with a mosaic karyotype and renal malformations (log XIAP –0.79±0.3 vs. –1.0±0.3, p=0.03). No correlations were seen between XIAP and other manifestations.Abnormal expression of XIAP may be an important underlying mechanism in the development of BAV and renal malformations in TS. However, abnormal XIAP mRNA expression, as determined from peripheral mononuclear cells, does not appear to explain all the somatic and visceral stigmata of TS.

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