Intra- and Interspecies Interactions between Prion Proteins and Effects of Mutations and Polymorphisms

Hundt, C.; Gauczynski, Sabine; Leucht, Christoph; Riley, Maria Louise; Weiß, Stefan

doi:10.1515/bc.2003.088

Cited by 20 publications

(17 citation statements)

References 65 publications

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“…In addition, Zahn's studies identified the OPRs' binding sites that are likely responsible for aggregation to span residues 60-91 of PrP C rather than regions flanking these residues. Whether the aggregation motifs are dimeric or oligomeric in nature is not known, but oligomerization of OPRs is consistent with yeast two-hybrid data provided by other investigators showing that OPRs interact with one another (Hundt et al 2003). Zahn's work reveals the significance of the in vitro functional presence of homooligomeric aggregation motifs in PrP C molecules.…”

Section: Introductionsupporting

confidence: 85%

The Role of the Prion Protein in the Molecular Basis for Synaptic Plasticity and Nervous System Development

et al. 2007

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It has been reported that unlike the more commonly expressed splice variants, the embryonic and stress-associated readthrough form of acetylcholinesterase (AChE-R) is unable to promote cell adhesion and neurite outgrowth. We investigated the possibility that the unique AChE-R C-terminal peptide (ARP) might be responsible for this difference, either by binding to AChE itself and inactivating the adhesion-mediating site or by competing with AChE for ligand binding. Synthetic peptides representing the ARP, a scrambled version of the ARP, and sequences of the previously identified adhesion-mediating site on AChE were used in in vitro binding and neuroblastoma cell-spreading assays. It was observed that the ARP was able to bind to laminin-1, identified previously as an in vitro AChE ligand and, to a lesser extent, to collagen IV and to AChE itself. ARP-AChE binding was, however, of very low affinity and was not significantly affected by peripheral site inhibitors, suggesting that inactivation of the AChE adhesion site is not the reason for AChE-R's antiadhesive character. On the other hand, the ARP competed with AChE and the adhesion site peptides for binding to laminin in vitro, and the ARP was observed to inhibit cell spreading in neuroblastoma cells grown on laminin. Monoclonal antibodies recognizing the known AChE adhesion site reacted with the ARP, suggesting structural similarities. These were borne out by an examination of sequence alignments of the ARP and the 28-53 AChE sequence. The ARP contains part of the PPxxxxRFxPPEP motif seen in AChEs and cholinesterase-domain proteins, and both it and the 37-53 sequence bear some resemblance to collagen and collagen-like proteins. It therefore appears likely that the ARP's structural similarity to the AChE adhesion-mediating site is the basis for the observed competition for ligand binding and might account for the antiadhesive characteristics of AChE-R.

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Section: Introductionsupporting

confidence: 85%

The Role of the Prion Protein in the Molecular Basis for Synaptic Plasticity and Nervous System Development

et al. 2007

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“…Also, PrP c dimerization activates signaling pathways and results in further clustering of the protein. Clustering is thus regarded as a sign of PrP c activation [17,31].Using an immunofluorescence method, we revealed the clustering of P-gp/PrP c complexes induced by paclitaxel. Antibodies that interfere with the function of P-gp also interfered with the formation of P-gp/PrP c clusters.…”

Section: Discussionmentioning

confidence: 96%

The role of P-glycoprotein/cellular prion protein interaction in multidrug-resistant breast cancer cells treated with paclitaxel

Cao

et al. 2008

Cell. Mol. Life Sci.

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We previously reported that treatment with P-glycoprotein (P-gp) substrates promotes in vitro invasion in multidrug-resistant (MDR) breast cancer cells. This effect is initiated by the P-gp pump function and mediated by interaction of P-gp with some unknown component(s). However, the underlying mechanism(s) remains poorly understood. Here we confirm a novel physical interaction between P-gp and cellular prion protein (PrP(c)). Blocking P-gp activity or depletion of PrP(c) inhibited paclitaxel (P-gp substrate)- induced invasion. Paclitaxel further facilitated the formation of P-gp/PrP(c) clusters residing in caveolar domains and promoted the association of P-gp with caveolin-1. Both caveolin-1 and the integrity of caveolae were required for the drug-induced invasion. In addition, the P-gp/PrP(c) complex also played an important role in anti-apoptotic activity of MCF7/Adr cells.These data provide new insights into the mode by which MDR breast cancers evade cytotoxic attacks from P-gp substrates and also suggest a role for P-gp/ PrP(c) interaction in this process.

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“…32,33 The exact mechanisms of metastasis are not well defined, but the propensity to metastasize is suggested to be related to HIF. 34,35 In some tumors, a positive association is observed between HIF-1α and tumor stage. 6,7,9,10 In renal cancer and neuroblastoma, however, HIF-2α but not HIF-1α promotes an aggressive phenotype.…”

Section: Discussionmentioning

confidence: 99%

HIF-1α and HIF-2α correlate with migration and invasion in gastric cancer

Wang¹,

Li²,

Zhang³

et al. 2010

Cancer Biology & Therapy

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Hypoxia-inducible factor-1 (HIF-1) is a major determinant of invasion and metastasis in several tumor types. We previously reported that HIF-1α contributed to multidrug resistance in gastric cancer. However, the role of HIF-2α on the progression of gastric cancer is seldom reported. In this study, we first examined the possible role of HIF-1α and HIF-2α in the process of invasiveness and metastasis of gastric cancer, using immunohistochemistry of 80 gastric cancer tissues, western blot and real-time PCR of 8 fresh gastric cancer tissues. The results showed that HIF-1α and HIF-2α were significantly correlated with the clinical stage and were highly expressed in metastatic gastric cancers compared to nonmetastatic ones. Western blot analysis revealed that hypoxia (1% O₂, 8 h) induced HIF-1α and HIF-2α expression in different gastric cancer cell lines, including SGC7901, AGS, MGC803 and MKN45. Adhesion and invasion assays found that hypoxia caused an increase in adhesive and invasive abilities of gastric cancer cells. Small interfering (si) RNA against HIF-1α and HIF-2α in SGC7901 cells significantly inhibited hypoxia-induced adhesive and invasive abilities. Finally, the JNK inhibitor SP 600125 abolished hypoxia-induced HIF-1α and HIF-2α expression, and inhibited the adhesive and invasive abilities of gastric cancer cells exposed to hypoxia in a dose-dependent manner. Taken together, the present work suggested that HIF-1α and HIF-2α were involved in metastasis and invasion of gastric cancer cells under hypoxia, with the involvement of JNK signal pathway.

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Intra- and Interspecies Interactions between Prion Proteins and Effects of Mutations and Polymorphisms

Cited by 20 publications

References 65 publications

The Role of the Prion Protein in the Molecular Basis for Synaptic Plasticity and Nervous System Development

The Role of the Prion Protein in the Molecular Basis for Synaptic Plasticity and Nervous System Development

The role of P-glycoprotein/cellular prion protein interaction in multidrug-resistant breast cancer cells treated with paclitaxel

HIF-1α and HIF-2α correlate with migration and invasion in gastric cancer

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