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Death à la carte
| Content Provider | Semantic Scholar |
|---|---|
| Author | Jackson, Thomas R. Larkin, Samantha E. T. Pickard, Olubukunola A. Townsend, Paul A. |
| Copyright Year | 2012 |
| Abstract | Delegates arrived at the hotel on a rainy Sunday evening where they were immediately made welcome and encouraged to relax over dinner while chatting to other EWCD (European Workshop on Cell Death) participants. The EWCD is a bi-annual conference that focuses on all aspects of cell death. Each conference is held in a different unique location, with this year’s being no exception. The six-day meeting took place in the Serre Chevalier Valley, France, in the picturesque village of Monêtierles-Bains. Over the course of the week there were sessions on the Bcl-2 family, death receptor signaling, pattern-recognition receptors and IAPs, XIAP and TNF, inflammation, autophagy, cell death and metabolism, mechanistic insights into tumorigenesis and tumor therapy. The conference opened with the Bcl-2 family session, chaired and introduced by Paul Ekert (Walter and Eliza Hall Institute). After introducing the session, he went on to discuss his work on the molecular mechanisms by which HoxA9 and HoxB8 overexpression can cause leukemia, in a Bcl-2-dependent and -independent manner respectively. After lunch, Conor Kearney, from Seamus Martin’s lab in Dublin, presented his work on TNF-induced cytokine production by inhibitors of apoptosis (IAPs). He presented his study of the immune consequences of small molecule IAP antagonists such as BV6. Previous studies found that IAP antagonism sensitizes tumor cells to TNF-induced apoptosis. Conor found that IAP antagonism also results in a dramatic modulation of many pro-inflammatory mediators, highlighting their possible role as regulators of inflammation. Later, Stephen Tait from the Beatson Institute, presented an exciting talk on RIP3K-mediated necroptosis. He used the E3 ubiquitin ligase, Parkin, to deplete cells of mitochondria through mitophagy. As expected, these mitochondrial depleted cells were not able to undergo apoptosis, but interestingly there was no clear inhibition of TNF-induced necroptosis. The day ended with the first of two poster sessions encompassing a wide range of cell death signaling topics. Seamus Martin began the next day with a session on inflammation. Seamus’s talk challenged the generally accepted paradigm that apoptosis is not pro-inflammatory, and is therefore “good,” whereas necroptosis is pro-inflammatory, so is thought to be “bad.” Seamus found that Fas/TRAIL/TNF stimulated apoptosis resulted in pro-inflammatory cytokine and chemokine (IL-6, CRCX1) production. Active discussion was stimulated by Yang Liu’s (University of Texas Southwestern Medical Center) presentation on the stimulation of autophagic cell death by an evolutionary conserved Beclin-1 peptide. Liu found that the Beclin-1 peptide (Tat-Beclin-1) was a potent inducer of autophagy, which was accompanied by cell death in the absence of caspase activation and was not rescued by apoptosis or necrosis inhibitors—a surprising observation that led to a lively debate. After lunch, Jennifer Martinez (St. Jude Children’s Research Hospital) presented her work on LC3-associated phagocytosis and IFN-a secretion. She demonstrated that stimulation of the autophagic and phagocytic pathways by DNA-containing immune complexes is necessary for TLR9-mediated production of IFN-a. The mechanism by which this occurs does not utilize the conventional autophagic pre-initiation complex. This work suggests a novel role for autophagy in response to inflammation. In the evening, the second of the poster sessions was held, which largely covered cell death in the context of therapy and tumorigenesis. The morning of the following day focused on new mechanistic insights into tumorigenesis. Sarah Pensa (University of Cambridge) spoke on the role of the JAK-STAT and PI3K pathways in mammary gland involution. Previous work had shown that STAT3 is required for non-classical lysosomalmediated cell death. Sarah reported the use of a microarray approach to identified two PI3K regulatory subunits, p50a and p55a, that were also STAT3 transcriptional targets. Mouse knockdowns demonstrated the importance of these subunits in mammary gland involution. Further, deregulation of Cathepsin B and L suggested a role of p50a/p55a in lysosomal-mediated cell death. Mikkel Rohde (Danish Cancer Society Research Center) previously identified siramesine as an inducer of lysosomal cell death in cancer. Here, he presented recent data *Correspondence to: Paul A. Townsend; Email: p.a.townsend@soton.ac.uk Submitted: 07/03/12; Accepted: 07/04/12 http://dx.doi.org/10.4161/jkst.21369 MEETING REPORT |
| Starting Page | 219 |
| Ending Page | 221 |
| Page Count | 3 |
| File Format | PDF HTM / HTML |
| Volume Number | 1 |
| Alternate Webpage(s) | http://ftp.ncbi.nlm.nih.gov/pub/pmc/2a/d1/jkst-1-219.PMC3670251.pdf |
| Journal | JAK-STAT |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
