http://hdl.handle.net/2440/11253 Sat, 25 May 2013 01:51:35 GMT 2013-05-25T01:51:35Z http://hdl.handle.net/2440/57828 Title: Solution structure and membrane interactions of the antimicrobial peptide Fallaxidin 4.1a: An NMR and QCM study Author: Sherman, Patrick James; Jackway, Rebecca Jo; Gehman, John D.; Praporski, Slavica; McCubbin, George A.; Mechler, Adam; Martin, Lisandra L.; Separovic, Frances; Bowie, John Hamilton Description: Copyright © 2009 American Chemical Society Wed, 31 Dec 2008 13:30:00 GMT http://hdl.handle.net/2440/57828 2008-12-31T13:30:00Z http://hdl.handle.net/2440/57698 Title: The HIF1 alpha-inducible pro-cell death gene BNIP3 is a novel target of SIM2s repression through cross-talk on the hypoxia response element; The HIF1α-inducible pro-cell death gene BNIP3 is a novel target of SIM2s repression through cross-talk on the hypoxia response element Author: Farrall, Alexandra Louise; Whitelaw, Murray Leslie Abstract: The short isoform of single-minded 2 (SIM2s), a basic helix–loop–helix/PAS (bHLH/PAS) transcription factor, is upregulated in pancreatic and prostate tumours; however, a mechanistic role for SIM2s in these cancers is unknown. Microarray studies in prostate DU145 cells identified the pro-cell death gene, BNIP3 (Bcl-2/adenovirus E1B 19 kDa interacting protein 3), as a novel putative target of SIM2s repression. Further validation showed BNIP3 repression in several prostate and pancreatic carcinoma-derived cell lines with ectopic expression of human SIM2s. BNIP3 levels are enhanced in prostate carcinoma cells upon short interfering (si)RNA-mediated knockdown of endogenous SIM2s. Chromatin immunoprecipitation and promoter studies show that SIM2s represses BNIP3 through its activities at the proximal promoter hypoxia response element (HRE), the site through which the bHLH/PAS family member, hypoxia-inducible factor 1α (HIF1α), induces BNIP3. SIM2s attenuates BNIP3 hypoxic induction via the HRE, and increased hypoxic induction of BNIP3 occurs with siRNA knockdown of endogenous SIM2s in prostate PC3AR+ cells. BNIP3 is implicated in hypoxia-induced cell death processes. Prolonged treatment of PC3AR+ cells with hypoxia mimetics, DP and DMOG, confers hypoxia-induced autophagy, measured by enhanced LC3-II levels and SQSTM1/p62 turnover. We show that PC3AR+ cells expressing ectopic SIM2s have enhanced survival in these conditions. Induction of LC3-II and turnover of SQSTM1/p62 are attenuated in PC3AR+/SIM2s DMOG and hypoxia-treated cells, suggesting that SIM2s may attenuate autophagic cell death processes, perhaps through BNIP3 repression. These data show, for the first time, SIM2s cross-talk on an endogenous HRE. SIM2s' functional interference with HIF1α activities on BNIP3 may indicate a novel role for SIM2s in promoting tumourigenesis. Description: © 2009 Macmillan Publishers Limited. All rights reserved Wed, 31 Dec 2008 13:30:00 GMT http://hdl.handle.net/2440/57698 2008-12-31T13:30:00Z http://hdl.handle.net/2440/56804 Title: Why do phage play dice? Author: Avlund, Mikkel; Dodd, Ian Burwell; Semsey, Szabolcs; Sneppen, Kim; Krishna, Sandeep Abstract: Phage lambda is among the simplest organisms that make a developmental decision. An infected bacterium goes either into the lytic state, where the phage particles rapidly replicate and eventually lyse the cell, or into a lysogenic state, where the phage goes dormant and replicates along with the cell. Experimental observations by P. Kourilsky are consistent with a single phage infection deterministically choosing lysis and double infection resulting in a stochastic choice. We argue that the phage are playing a "game" of minimizing the chance of extinction and that the shift from determinism to stochasticity is due to a shift from a single-player to a multiplayer game. Crucial to the argument is the clonal identity of the phage. Description: Copyright © 2009, American Society for Microbiology. All Rights Reserved. Wed, 31 Dec 2008 13:30:00 GMT http://hdl.handle.net/2440/56804 2008-12-31T13:30:00Z http://hdl.handle.net/2440/53277 Title: The bHLH/Per-Arnt-Sim transcription factor SIM2 regulates muscle transcript myomesin2 via a novel, non-canonical E-box sequence Author: Woods, Susan Lesley; Farrall, Alexandra Louise; Procko, Carl; Whitelaw, Murray Leslie Abstract: Despite a growing number of descriptive studies that show Single-minded 2 (Sim2) is not only essential for murine survival, but also upregulated in colon, prostate and pancreatic tumours, there is a lack of direct target genes identified for this basic helix–loop–helix/PAS transcription factor. We have performed a set of microarray experiments aimed at identifying genes that are differentially regulated by SIM2, and successfully verified that the Myomesin2 (Myom2) gene is SIM2-responsive. Although SIM2 has been reported to be a transcription repressor, we find that SIM2 induces transcription of Myom2 and activates the Myom2 promoter sequence when co-expressed with the heterodimeric partner protein, ARNT1, in human embryonic kidney cells. Truncation and mutation of the Myom2 promoter sequence, combined with chromatin immunoprecipitation studies in cells, has lead to the delineation of a non-canonical E-box sequence 5'-AACGTG-3' that is bound by SIM2/ARNT1 heterodimers. Interestingly, in immortalized human myoblasts knock down of Sim2 results in increased levels of Myom2 RNA, suggesting that SIM2 is acting as a repressor in these cells and so its activity is likely to be highly context dependent. This is the first report of a direct SIM2/ARNT1 target gene with accompanying analysis of a functional response element. Mon, 31 Dec 2007 13:30:00 GMT http://hdl.handle.net/2440/53277 2007-12-31T13:30:00Z