Febs Letters

doi: 10.1016/S0014-5793(08)00723-0pmid: N/A

Gonzalez-Romero, Dennisse; Barria, Marcelo A.; Leon, Patricia; Morales, Rodrigo; Soto, Claudio

doi: 10.1016/j.febslet.2008.08.003pmid: 18706416

Prions are the infectious agents responsible for prion diseases, which appear to be composed exclusively by the misfolded prion protein (PrPSc). The mechanism of prion transmission is unknown. In this study, we attempted to detect prions in urine of experimentally infected animals. PrPSc was detected in ∼80% of the animals studied, whereas no false positives were observed among the control animals. Semi‐quantitative calculations suggest that PrPSc concentration in urine is around 10‐fold lower than in blood. Interestingly, PrPSc present in urine maintains its infectious properties. Our data indicate that low quantities of infectious prions are excreted in the urine. These findings suggest that urine is a possible source of prion transmission.

Luu, Tony C.; Bhattacharya, Pompeya; Chan, William K.

doi: 10.1016/j.febslet.2008.08.007pmid: 18708059

Cyclophilin‐40 (CyP40) promotes the formation of the gel shift complex that contains the aryl hydrocarbon receptor (AhR), AhR nuclear translocator (Arnt) and dioxin response element (DRE) using baculovirus expressed proteins. Here we reported that CyP40 plays a role in the AhR signaling. When the CyP40 content in MCF‐7 cells is reduced, up‐regulation of cyp1a1 and cyp1b1 by 3‐methylchloranthrene (3MC) is also reduced, suggesting that CyP40 is essential for maximal AhR function. The CyP40 region containing amino acids 186–215, but not the peptidyl‐prolyl cis–trans isomerase and tetratricopeptide repeat domains, is essential for forming the AhR/Arnt/DRE complex. CyP40 is found in the cell nucleus after 3MC treatment and appears to promote the DRE binding form of the AhR/Arnt heterodimer.

Weisshaar, Stefan R.; Keusekotten, Kirstin; Krause, Anke; Horst, Christiane; Springer, Helen M.; Göttsche, Kerstin; Dohmen, R. Jürgen; Praefcke, Gerrit J.K.

doi: 10.1016/j.febslet.2008.08.008pmid: 18708055

We have recently reported that poly‐SUMO‐2/3 conjugates are subject to a ubiquitin‐dependent proteolytic control in human cells. Here we show that arsenic trioxide (ATO) increases SUMO‐2/3 modification of promyelocytic leukemia (PML) leading to its subsequent ubiquitylation in vivo. The SUMO‐binding ubiquitin ligase RNF4 mediates this modification and causes disruption of PML nuclear bodies upon treatment with ATO. Reconstitution of SUMO‐dependent ubiquitylation of PML by RNF4 in vitro and in a yeast trans vivo system revealed a preference of RNF4 for chain forming SUMOs. Polysumoylation of PML in response to ATO thus leads to its recognition and ubiquitylation by RNF4.

Awe, Karin; Lambert, Carsten; Prange, Reinhild

doi: 10.1016/j.febslet.2008.07.062pmid: 18708056

The hepatitis B virus L protein forms a dual topology in the endoplasmic reticulum (ER) via a process involving cotranslational membrane integration and subsequent posttranslational translocation of its preS subdomain. Here, we show that preS posttranslocation depends on the action of the ER chaperone BiP. To modulate the in vivo BiP activity, we designed an approach based on overexpressing its positive and negative regulators, ER‐localized DnaJ‐domain containing protein 4 (ERdj4) and BiP‐associated protein (BAP), respectively. The feasibility of this approach was confirmed by demonstrating that BAP, but not ERdj4, destabilizes the L/BiP complex. Overexpressing BAP or ERdj4 inhibits preS posttranslocation as does the reduction of ATP levels. These results hint to a new role of BiP in guiding posttranslational polypeptide import into the mammalian ER.

Wan, Bingbing; Zhou, Yu-Bo; Zhang, Xin; Zhu, Hong; Huo, Keke; Han, Ze-Guang

doi: 10.1016/j.febslet.2008.08.009pmid: 18708057

We describe a novel secreted protein, named hOLFML1 (human olfactomedin‐like protein 1), with an olfectamine domain in its C‐terminus, mainly expressed in the small intestine, liver, lung and heart. Immunohistochemical staining on human small intestine indicated that the protein localizes preferentially in the intestinal villi. Interestingly, ectopic hOLFML1 promoted proliferation of HeLa cells and increased the percentage of cells in S phase. In contrast, knock down of hOLFML1 protein expression by siRNA inhibited cell proliferation and delayed the entry of cells into S phase. Our data also revealed that hOLFML1 is N‐glycosylated and its secretion is triggered by serum. Taken together, these findings suggest that hOLFML1 may play a significant role in the regulation of cell proliferation in vitro.

Bhat, Krishna P.; Pelloski, Christopher E.; Zhang, Yujian; Kim, Se Hoon; deLaCruz, Clarissa; Rehli, Michael; Aldape, Kenneth D.

doi: 10.1016/j.febslet.2008.08.010pmid: 18708058

Here we show that in contrast to other cancer types, tumor necrosis factor (TNF)‐α suppresses YKL‐40 expression in glioma cell lines in a nuclear factor κB (NF‐κB) dependent manner. Even though TNF‐α causes recruitment of p65 and p50 subunits of NF‐κB to the YKL‐40 promoter in all cell types, recruitment of histone deacetylases (HDAC)‐1 and ‐2, and a consequent deacetylation of histone H3 at the YKL‐40 promoter occurs only in glioma cells. Importantly, using chromatin immunoprecipitation assays in frozen glioblastoma multiforme tissues, we show that YKL‐40 levels decrease consistent with HDAC1 recruitment despite high levels of nuclear p‐p65. This study presents a paradigm for NF‐κB regulation of one of its targets in a strict cell type specific manner.

Nishizuka, Makoto; Koyanagi, Akiko; Osada, Shigehiro; Imagawa, Masayoshi

doi: 10.1016/j.febslet.2008.08.011pmid: 18708054

The roles of the non‐canonical Wnt pathway during adipogenesis are not well known, though Wnt10b is known to function as a negative regulator for adipogenesis by activating the canonical Wnt pathway. We focused on the roles of Wnt4, Wnt5a and Wnt6, which are thought to be part of the non‐canonical Wnt pathway. The expression of these genes changed dramatically at the initial stage of adipogenesis. Furthermore, the inhibition of Wnt4 or Wnt5a expression prevented the accumulation of triacylglycerol and decreased the expression of adipogenesis‐related genes. Wnt4 and Wnt5a have crucial roles in adipogenesis as positive regulators.

HuangFu, Wei-Chun; Liu, Jianghuai; Harty, Ronald N.; Fuchs, Serge Y.

doi: 10.1016/j.febslet.2008.08.013pmid: 18722370

While negative effect of smoking on the resistance to viral infections was known, the underlying mechanisms remained unclear. Here we report that products of cigarette smoking compromise the cellular anti‐viral defenses by inhibiting the signaling induced by Type I interferon (IFN). Cigarette smoking condensate (but not pure nicotine) stimulated specific serine phosphorylation‐dependent ubiquitination and degradation of the IFNAR1 subunit of the Type I IFN receptor leading to attenuation of IFN signaling and decreased resistance to viral infection. This resistance was restored in cells where phosphorylation‐dependent degradation of IFNAR1 is abolished. We conclude that smoking compromises cellular anti‐viral defenses via degradation of Type I IFN receptor and discuss the significance of this mechanism for efficacy of IFN‐based therapies.

Cheng, Lin; Lin, Hui; Fan, Xuelian; Qiu, Shi; Sun, Tao; Li, Tai-Yuan; Zhang, Yi

doi: 10.1016/j.febslet.2008.08.012pmid: 18722371

Here we report a toxin–antitoxin (TA) operon talAB identified from the Gram‐positive bacterium Leifsonia xyli subsp. cynodontis. It is shown that talB encodes a broad‐host cytotoxin functioning in different Gram‐positive bacteria, while talA encodes its antidote. TalA and TalB form different hetero‐oligomers in vitro; these hetero‐oligomers, but not the antitoxin TalA, strongly bind to the talAB promoter region containing two inverted repeats. This represents a new mechanism of binding the promoter of a TA operon by the toxin and antitoxin complexes.