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174 Newest Publications of Portland Press

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A context-independent N-glycan signal targets the misfolded extracellular domain of Arabidopsis STRUBBELIG to endoplasmic-reticulum-associated degradation

15-12-2014 | Huttner S; Veit C; Vavra U; Schoberer J; Dicker M; Maresch D; Altmann F; Strasser R, Biochemical Journal, 2014

N-glycosylation of proteins plays an important role in the determination of the fate of newly synthesized glycoproteins in the endoplasmic reticulum (ER). Specific oligosaccharide structures recruit molecular chaperones that promote folding or mannose-binding lectins that assist in the clearance ...

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The function of phosphatidylinositol 5-phosphate 4-kinase {gamma}(PI5P4K{gamma}) explored using a specific inhibitor that targets the PI5P binding site.

11-12-2014 | Clarke J; Giudici M; Burke J; Williams R; Maloney D; Marugan J; Irvine R, Biochemical Journal, 2014

NIH-12848 (NCGC00012848-02), a putative phosphatidylinositol-5-phosphate 4-kinase γ (PI5P4Kγ) inhibitor, was explored as a tool for investigating this enigmatic, low activity, lipid kinase. PI5P 4-kinase assays in vitro showed that NIH-12848 inhibited PI5P4Kγ with an IC50 of approximately 1μM but ...

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Cinderella finds her shoe: the first Vps34 inhibitor uncovers a new PI3K-AGC protein kinase connection

01-12-2014 | Bilanges B; Vanhaesebroeck B, Biochemical Journal, 2014

Class II/III PI3Ks (phosphoinositide 3-kinases) produce the PtdIns(3)P lipid that is involved in intracellular vesicular trafficking. In contrast with class I PI3Ks, the potential signalling roles of class II/III PI3Ks are poorly understood. In a recent article in the Biochemical Journal, Bago ...

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Identification of key binding site residues of MCT1 for AR-C155858 reveals the molecular basis of its isoform selectivity

01-12-2014 | Nancolas B; Sessions R; Halestrap A, Biochemical Journal, 2014

The proton-linked monocarboxylate transporters (MCTs) are required for lactic acid transport into all mammalian cells. Thus they play an essential role in tumour cells that are usually highly glycolytic and are promising targets for anti-cancer drugs. AR-C155858 is a potent MCT1 inhibitor (Ki ~ 2 ...

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Ubiquitination profiling identifies sensitivity factors for IAP antagonist treatment

21-11-2014 | Varfolomeev E; Izrael-Tomasevic A; Yu K; Bustos D; Goncharov T; Belmont L; Masselot A; Bakalarski C; Kirkpatrick D; ..., Biochemical Journal, 2014

Evasion of cell death is one crucial capability acquired by tumor cells to ward off anti-tumor therapies, and represents a fundamental challenge to sustaining clinical efficacy for currently available agents. Inhibitor of Apoptosis (IAP) proteins use their ubiquitin E3 ligase activity to promote ...

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Calcium-Ask1-MKK7-JNK2-c-Src Signaling Cascade Mediates Disruption of Intestinal Epithelial Tight Junctions by Dextran Sulfate Sodium

07-11-2014 | Samak G; Chaudhry K; Gangwar R; Narayanan D; Jaggar J; Rao R, Biochemical Journal, 2014

Disruption of intestinal epithelial tight junctions is an important event in the pathogenesis of ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis in mice with the symptoms similar to ulcerative colitis. However, the mechanism of DSS-induced colitis is unknown. We investigated the ...

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The role of Ca{Less than}sup{Greater than}2{+}{Less than}/sup{Greater than} influx in endocytic vacuole formation in pancreatic acinar cells

05-11-2014 | Voronina S; Collier D; Chvanov M; Middlehurst B; Beckett A; Prior I; Criddle D; Begg M; Mikoshiba K; Sutton R; Tepikin A, Biochemical Journal, 2014

The inducers of acute pancreatitis trigger a prolonged increase in the cytosolic Ca2+ concentration, which is responsible for the damage and eventual death of pancreatic acinar cells. Vacuolisation is an important indicator of pancreatic acinar cell damage. Furthermore, activation of trypsinogen ...

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Circular trimers of gelatinase B/ matrix metalloproteinase-9 constitute a distinct population of functional enzyme molecules differentially regulated by tissue inhibitor of metalloproteinases-1

31-10-2014 | Vandooren J; Born B; Solomonov I; Zajac E; Saldova R; Senske M; Ugarte-Berzal E; Martens E; Van den Steen P; Van Dam ..., Biochemical Journal, 2014

Gelatinase B/ matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) cleaves many substrates and is produced by most cell types as a zymogen, proMMP-9, in complex with the tissue inhibitor of metalloproteinases-1 (TIMP-1). Natural proMMP-9 occurs as monomers, homomultimers, and heterocomplexes, but ...

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Exchange Protein Directly Activated by cAMP (EPAC1) Modulates Regulatory T Cell-Mediated Immune Suppression

23-10-2014 | Almahariq M; Mei F; Wang H; Cao A; Yao S; Soong L; Sun J; Cong Y; Chen J; Cheng X, Biochemical Journal, 2014

The cyclic adenosine monophosphate (cAMP) signaling pathway plays an essential role in immune functions. In this study we examined the role of the cAMP/EPAC1 (exchange protein directly activated by cAMP) axis in regulatory T-cell (Treg)-mediated immune suppression using genetic and pharmacologic ...

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p58(IPK) is an Inhibitor of the eIF2{alpha} Kinase GCN2 and its Localisation and Expression Underpin Protein Synthesis and ER Processing Capacity

20-10-2014 | Roobol A; Roobol J; Bastide A; Knight J; Willis A; Smales C, Biochemical Journal, 2014

One of the key cellular responses to stress is the attenuation of mRNA translation and protein synthesis via the phosphorylation of eIF2α. This is mediated by four eIF2α kinases and it has been suggested that each kinase is specific to the cellular stress imposed. Herein we show that both PERK ...

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