Dual Role of BRUCE as an Antiapoptotic IAP and a Chimeric E2/E3 Ubiquitin Ligase

Bartke, Till; Pohl, Christian; Pyrowolakis, George; Jentsch, Stefan

doi:10.1016/j.molcel.2004.05.018

Cited by 201 publications

(250 citation statements)

References 28 publications

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“…Caspase-2 localizes to the Golgi as well as the nucleus (Mancini et al, 2000;O'Reilly et al, 2002). Apollon, an inhibitor of apoptosis protein, has been reported to be Golgi localized (Hauser et al, 1998;Bartke et al, 2004;Hao et al, 2004). The death receptor adaptor protein TNF-receptor-associated death domain-containing protein also shows localization to the Golgi (Jones et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Maag

Mancini

Rosen

et al. 2005

MBoC

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Golgin-160 is a coiled-coil protein on the cytoplasmic face of the Golgi complex that is cleaved by caspases during apoptosis. We assessed the sensitivity of cell lines stably expressing wild-type or caspase-resistant golgin-160 to several proapoptotic stimuli. Cells expressing a caspase-resistant mutant of golgin-160 were strikingly resistant to apoptosis induced by ligation of death receptors and by drugs that induce endoplasmic reticulum (ER) stress, including brefeldin-A, dithiothreitol, and thapsigargin. However, both cell lines responded similarly to other proapoptotic stimuli, including staurosporine, anisomycin, and etoposide. The caspase-resistant golgin-160 dominantly prevented cleavage of endogenous golgin-160 after ligation of death receptors or induction of ER stress, which could be explained by a failure of initiator caspase activation. The block in apoptosis in cells expressing caspase-resistant golgin-160 could not be bypassed by expression of potential caspase cleavage fragments of golgin-160, or by drug-induced disassembly of the Golgi complex. Our results suggest that some apoptotic signals (including those initiated by death receptors and ER stress) are sensed and integrated at Golgi membranes and that golgin-160 plays an important role in transduction of these signals. INTRODUCTIONThe Golgi complex is central to the regulation of membrane trafficking in eukaryotic cells. It is the primary site for sorting and processing of proteins undergoing both exocytosis and endocytosis (reviewed in Farquhar and Palade, 1998). Under normal conditions, the mammalian Golgi complex is a collection of stacks of cisternal membranes near the microtubule organizing center. Proteins traversing the secretory pathway enter the Golgi at the cis face, are processed as they pass through the Golgi stacks, and are sorted at the trans face into vesicles bound for their intended destinations. The trans-Golgi is also important in sorting proteins being endocytosed or cycling between the plasma membrane and intracellular membrane compartments. This affords the Golgi extensive communication with the rest of the cell and its surroundings, placing it in a prime position to sense and integrate information about the state of the cell and its environment.The structure of the Golgi is highly dynamic, allowing reversible disassembly during mitosis. Key secretory pathway proteins are phosphorylated in a cell cycle-dependent manner to stop membrane trafficking and disassemble the Golgi (reviewed in Rabouille and Jokitalo, 2003). This rearrangement from a single perinuclear organelle to dispersed vesiculated compartments is thought to ensure partitioning of the Golgi complex into both daughter cells during cytokinesis. When Golgi disassembly is prevented by addition of antibodies to Golgi reassembly and stacking protein of 65 kDa (GRASP65), cells complete S phase, but they are unable to enter mitosis. This mitotic block can be bypassed by disassembling the Golgi with drugs (Sutterlin et al., 2002). Once mitosis is complete, the Golgi...

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Section: Discussionmentioning

confidence: 99%

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Maag

Mancini

Rosen

et al. 2005

MBoC

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“…14 Several lines of evidence show that the Apollon can protect cells against apoptosis and functions as an IAP by binding the active caspases via its single BIR domain. [16][17][18] Furthermore, studies also show that Apollon can promote ubiquitination of the IAP antagonist Smac, which depends on the integrity of both the catalytically active ubiquitin-conjugating domain and the correctly folded BIR domain. [16][17][18] Apollon is upregulated in some drug-resistant cancer cells, and antisense oligonucleotides against Apollon significantly sensitizes tumor cells to apoptosis induced by chemotherapy agents.…”

Section: Introductionmentioning

confidence: 99%

“…[16][17][18] Furthermore, studies also show that Apollon can promote ubiquitination of the IAP antagonist Smac, which depends on the integrity of both the catalytically active ubiquitin-conjugating domain and the correctly folded BIR domain. [16][17][18] Apollon is upregulated in some drug-resistant cancer cells, and antisense oligonucleotides against Apollon significantly sensitizes tumor cells to apoptosis induced by chemotherapy agents. 13 These findings suggest that Apollon has an antiapoptotic role and has been considered to be an attractive target with respect to molecular therapy of cancer.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic adenovirus-mediated shRNA against Apollon inhibits tumor cell growth and enhances antitumor effect of 5-fluorouracil

Chu

Sun

et al. 2008

Gene Ther

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Apollon, a membrane-associated inhibitor of apoptosis protein, protects cells against apoptosis and is upregulated in certain tumor cells. In this study, the effects of Apollon protein knockdown by RNA interference on the growth of human HeLa, HT-1080 and MCF-7 cells in vitro and in vivo were investigated. An oncolytic adenovirus (ZD55) containing the RNA polymerase III-dependent U6 promoter to express short hairpin RNA (shRNA) directed against Apollon (ZD55-siApollon) was constructed. Our data show that ZD55-siApollon successfully exerts a gene knockdown effect and causes the inhibition of tumor cell growth both in culture and in athymic mice in vivo. Cell cycle analysis, 4 0 ,6-diamidino-2-phenylindole staining and western blot analysis reveal that ZD55-siApollon-mediated suppression of Apollon induces apoptosis. Intratumoral injection of ZD55-siApollon significantly inhibits tumor growth in HT-1080 xenograft mice. Furthermore, ZD55-siApollon enhances the antitumor effect of 5-fluorouracil, a chemotherapeutic agent. In conclusion, these results suggest that the depletion of Apollon by oncolytic adenovirus-shRNA delivery system provides a promising method for cancer therapy.

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“…The putative UBC enzyme UBE2O, together with BRUCE [19,20], constitute the two large E2 enzymes. UBE2O was first purified from rabbit reticulocytes and named as E2-230K [19].…”

Section: Introductionmentioning

confidence: 99%

UBE2O negatively regulates TRAF6-mediated NF-κB activation by inhibiting TRAF6 polyubiquitination

Zhang

et al. 2013

Cell Res

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Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is a key regulator of the activation of transcription factor NF-κB by the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily. Recruitment of TRAF6 to the receptor-associated IRAK1-IRAK4-MyD88 adaptor protein complex induces lysine 63 (K63) autopolyubiquitination of TRAF6, which leads to further recruitment of downstream regulators, such as TAB2/3 and TAK1, and subsequently triggers NF-κB activation. Here, we identified the putative E2 ubiquitin-conjugating (UBC) enzyme UBE2O as a novel negative regulator of TRAF6-dependent NF-κB signaling. We found that UBE2O binds to TRAF6 to inhibit its K63-polyubiquitination, and to prevent the activation of NF-κB by IL-1β and lipopolysaccharides (LPS). We further show that the inhibitory effect of UBE2O is independent of its carboxy-terminal UBC domain. In contrast, we found that UBE2O acts to disrupt the IL-1β-induced association of TRAF6 with MyD88. These results provide novel insight into the regulation of signaling by IL-1R/TLR and TRAF6.

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Dual Role of BRUCE as an Antiapoptotic IAP and a Chimeric E2/E3 Ubiquitin Ligase

Cited by 201 publications

References 28 publications

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Oncolytic adenovirus-mediated shRNA against Apollon inhibits tumor cell growth and enhances antitumor effect of 5-fluorouracil

UBE2O negatively regulates TRAF6-mediated NF-κB activation by inhibiting TRAF6 polyubiquitination

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